Sample records for activated fatty acids

Peroxisome proliferators such as clofibric acid, nafenopin, and WY-14,643 have been shown to activate peroxisome proliferator-activated receptor (PPAR), a member of the steroid nuclear receptor superfamily. We have cloned the cDNA from rat that is homologous to that from mouse, which encodes a 97% similar protein. To search for physiologically occurring activators, we established a transcriptional transactivation assay by stably expressing in CHO cells a chimera of rat PPAR and the human glucocorticoid receptor that activates expression of the placental alkaline phosphatase reporter gene under the control of the mouse mammary tumor virus promoter. 150 microM concentrations of arachidonic or linoleic acid but not of dehydroepiandrosterone, cholesterol, or 25-hydroxy-cholesterol, activated the receptor chimera. In addition, saturated fattyacids induced the reporter gene. Shortening the chain length to n = 6 or introduction of an omega-terminal carboxylic group abolished the activation potential of the fattyacid. To test whether a common PPAR binding metabolite might be formed from free fattyacids we tested the effects of differentially beta-oxidizable fattyacids and inhibitors of fattyacid metabolism. The peroxisomal proliferation-inducing, non-beta-oxidizable, tetradecylthioacetic acidactivated PPAR to the same extent as the strong peroxisomal proliferator WY-14,643, whereas the homologous beta-oxidizable tetradecylthiopropionic acid was only as potent as a non-substituted fattyacid. Cyclooxygenase inhibitors, radical scavengers or cytochrome P450 inhibitors did not affect activation of PPAR. In conclusion, beta-oxidation is apparently not required for the formation of the PPAR-activating molecule and this moiety might be a fattyacid, its ester with CoA, or a further derivative of the activatedfattyacid prior to beta-oxidation of the acyl-CoA ester. PMID:7626496

In the search of value-added products from surplus soybean oil, we produced many new hydroxy fattyacids through microbial bioconversion. Hydroxy fattyacids are used in a wide range of industrial products, such as resins, waxes, nylons plastics, lubricants, cosmetics, and additives in coatings and...

The fattyacid alcohol ester-synthesizing activity of lipoprotein lipase (LPL) was characterized using bovine milk LPL. Synthesizing activities were determined in an aqueous medium using oleic acid or trioleylglycerol as the acyl donor and equimolar amounts of long-chain alcohols as the acyl acceptor. When oleic acid and hexadecanol emulsified with gum arabic were incubated with LPL, palmityl oleate was synthesized, in a time- and dose-dependent manner. Apo-very low density lipoprotein (apoVLDL) stimulated LPL-catalyzed palmityl oleate synthesis. The apparent equilibrium ratio of fattyacid alcohol ester/oleic acid was estimated using a high concentration of LPL and a long (20 h) incubation period. The equilibrium ratio was affected by the incubation pH and the alcohol chain length. When the incubation pH was below pH 7.0 and long chain fatty acyl alcohols were used as substrates, the fattyacid alcohol ester/free fattyacid equilibrium ratio favored ester formation, with an apparent equilibrium ratio of fattyacid alcohol ester/fattyacid of about 0.9/0.1. The equilibrium ratio decreased sharply at alkaline pH (above pH 8.0). The ratio also decreased when fatty alcohols with acyl chains shorter than dodecanol were used. When a trioleoylglycerol/fatty acyl alcohol emulsion was incubated with LPL, fattyacid alcohol esters were synthesized in a dose- and time-dependent fashion. Fattyacid alcohol esters were easily synthesized from trioleoylglycerol when fatty alcohols with acyl chains longer than dodecanol were used, but synthesis was decreased with fatty alcohols with acyl chain lengths shorter than decanol, and little synthesizing activity was detected with shorter-chain fatty alcohols such as butanol or ethanol. PMID:10578059

These studies defined the expression patterns of genes involved in fattyacid transport, activation and trafficking using quantitative PCR (qPCR) and established the kinetic constants of fattyacid transport in an effort to define whether vectorial acylation represents a common mechanism in different cell types (3T3-L1 fibroblasts and adipocytes, Caco-2 and HepG2 cells and three endothelial cell lines (b-END3, HAEC, and HMEC)). As expected, fattyacid transport protein (FATP)1 and long-chain acyl CoA synthetase (Acsl)1 were the predominant isoforms expressed in adipocytes consistent with their roles in the transport and activation of exogenous fattyacids destined for storage in the form of triglycerides. In cells involved in fattyacid processing including Caco-2 (intestinal-like) and HepG2 (liver-like), FATP2 was the predominant isoform. The patterns of Acsl expression were distinct between these two cell types with Acsl3 and Acsl5 being predominant in Caco-2 cells and Acsl4 in HepG2 cells. In the endothelial lines, FATP1 and FATP4 were the most highly expressed isoforms; the expression patterns for the different Acsl isoforms were highly variable between the different endothelial cell lines. The transport of the fluorescent long-chain fattyacid C(1)-BODIPY-C(12) in 3T3-L1 fibroblasts and 3T3-L1 adipocytes followed typical Michaelis-Menten kinetics; the apparent efficiency (k(cat)/K(T)) of this process increases over 2-fold (2.1 x 10(6)-4.5 x 10(6)s(-1)M(-1)) upon adipocyte differentiation. The V(max) values for fattyacid transport in Caco-2 and HepG2 cells were essentially the same, yet the efficiency was 55% higher in Caco-2 cells (2.3 x 10(6)s(-1)M(-1) versus 1.5 x 10(6)s(-1)M(-1)). The kinetic parameters for fattyacid transport in three endothelial cell types demonstrated they were the least efficient cell types for this process giving V(max) values that were nearly 4-fold lower than those defined form 3T3-L1 adipocytes, Caco-2 cells and HepG2 cells. The

In the work, the in vitro antiproliferative activity of a series of synthetic fattyacid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fattyacid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer. PMID:25510639

Background Direct conversion of solar energy and carbon dioxide to drop in fuel molecules in a single biological system can be achieved from fattyacid-based biofuels such as fatty alcohols and alkanes. These molecules have similar properties to fossil fuels but can be produced by photosynthetic cyanobacteria. Results Synechocystis sp. PCC6803 mutant strains containing either overexpression or deletion of the slr1609 gene, which encodes an acyl-ACP synthetase (AAS), have been constructed. The complete segregation and deletion in all mutant strains was confirmed by PCR analysis. Blocking fattyacidactivation by deleting slr1609 gene in wild-type Synechocystis sp. PCC6803 led to a doubling of the amount of free fattyacids and a decrease of alkane production by up to 90 percent. Overexpression of slr1609 gene in the wild-type Synechocystis sp. PCC6803 had no effect on the production of either free fattyacids or alkanes. Overexpression or deletion of slr1609 gene in the Synechocystis sp. PCC6803 mutant strain with the capability of making fatty alcohols by genetically introducing fatty acyl-CoA reductase respectively enhanced or reduced fatty alcohol production by 60 percent. Conclusions Fattyacidactivation functionalized by the slr1609 gene is metabolically crucial for biosynthesis of fattyacid derivatives in Synechocystis sp. PCC6803. It is necessary but not sufficient for efficient production of alkanes. Fatty alcohol production can be significantly improved by the overexpression of slr1609 gene. PMID:22433663

Using a luciferase reporter gene assay, we identified polyunsaturated fattyacids (PUFA) to impair NF kappaB signaling. Furthermore, we could demonstrate the PUFA ability to derogate NF kappaB activity to be independent from the family the fattyacid belongs to. Instead, we found a relation between the number of bis-allyl-methylene positions of the PUFA added and the NF kappaB activity of stimulated, long-term supplemented cells. The data presented provide new insights into the biological mechanisms PUFA exert their anti-inflammatory effects. Since suppression of NF kappaB activity could be of benefit in a number of inflammatory diseases as well as cancer, our findings are of clinical implication. According to our data dietary supplementation with PUFA-containing oils is likely to provide an at least palliative therapy for disorders linked to inappropriate NF kappaB signaling. PMID:20580946

Considering the therapeutic potential of fattyacid amides, the present study aimed to evaluate their in vitro activity against Toxocara canis larvae and their cytotoxicity for the first time. Linoleylpyrrolidilamide was the most potent, with a minimal larvicidal concentration (MLC) of 0.05 mg/mL and 27% cytotoxicity against murine peritoneal macrophages C57BL/6 mice, as assessed by the MTT assay. PMID:26783180

The “RNA world” and the “Lipid world” theories for the origin of cellular life are often considered incompatible due to the differences in the environmental conditions at which they can emerge. One obstacle resides in the conflicting requirements for divalent metal ions, in particular Mg2+, with respect to optimal ribozyme activity, fattyacid vesicle stability and protection against RNA strand cleavage. Here, we report on the activity of a short L1 ligase ribozyme in the presence of myristoleic acid (MA) vesicles at varying concentrations of Mg2+. The ligation rate is significantly lower at low-Mg2+ conditions. However, the loss of activity is overcompensated by the increased stability of RNA leading to a larger amount of intact ligated substrate after long reaction periods. Combining RNA ligation assays with fattyacid vesicles we found that MA vesicles made of 5 mM amphiphile are stable and do not impair ligase ribozyme activity in the presence of approximately 2 mM Mg2+. These results provide a scenario in which catalytic RNA and primordial membrane assembly can coexist in the same environment. PMID:25513761

A microsomal fattyacid elongase activity measured in epidermis of rapidly expanding leek (Allium porrum L.) was 10-fold higher in specific activity than preparations from store-bought leek. These preparations elongated acyl chains effectively using endogenous or supplied primers. Elongation of C20:0 was specifically inhibited by 2 [mu]M cerulenin, and labeling experiments with [3H]cerulenin labeled two polypeptides (65 and 88 kD). ATP was required for maximal elongase activity in expanding leaves but was lost in nonexpanding tissues. Both [14C]stearoyl-coenzyme A (CoA) and [14C]stearate were maximally elongated in the presence of ATP. Addition of fully reduced CoA, however, inhibited [14C]stearate elongation, suggesting that stearoyl-CoA synthesis was not a prerequisite for elongation. Furthermore, microsomes preincubated with [14C]stearoyl-CoA plus ATP resulted in loss of radiolabel from the acyl-CoA pool without a corresponding loss in elongating activity. The lack of correlation between elongating activity and the label retained in the putative acyl-CoA substrate pool suggests that acyl-CoAs may not be the immediate precursors for elongation and that ATP plays a critical, yet undefined, role in the elongation process. We propose that an ATP-dependent elongating activity may generate the long-chain fattyacids required for wax biosynthesis. PMID:12228624

Background fattyacids are considered to be effective components to promote wound healing and Lucilia sericata larvae are applied clinically to treat intractable wounds. We aimed to investigat the effect of fattyacid extracts from dried Lucilia sericata larvae on murine cutaneuous wound healing as well as angiogenesis. Results On day 7 and 10 after murine acute excision wounds creation, the percent wound contraction of fattyacid extracts group was higher than that of vaseline group. On day 3, 7 and 10 after wounds creation, the wound healing quality of fattyacid extracts group was better than that of vaseline group on terms of granulation formation and collagen organization. On day 3 after wounds creation, the micro vessel density and vascular endothelial growth factor expression of fattyacid extracts group were higher than that of vaseline group. Component analysis of the fattyacid extracts by gas chromatography-mass spectrometry showed there were 10 kinds of fattyacids in total and the ratio of saturated fattyacid, monounsaturated fattyacid and polyunsaturated fattyacid (PUFA) was: 20.57%:60.32%:19.11%. Conclusions Fattyacid extracts from dried Lucilia sericata larvae, four fifths of which are unsaturated fattyacids, can promote murine cutaneous wound healing probably resulting from the powerful angiogenic activity of the extracts. PMID:20211009

The present invention relates to a method for producing mutants of a fattyacid desaturase having a substantially increased activity towards fattyacid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fattyacid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fattyacids, thereby selecting for recipient cells which have received and which express a mutant fattyacid desaturase with an elevated specificity for fattyacid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fattyacid products.

Acetyl CoA carboxylase (ACC1 & ACC2) generates malonyl CoA, a substrate for de novo lipogenesis (DNL) and an inhibitor of mitochondrial fattyacid β-oxidation (FAO). Malonyl CoA is also a substrate for microsomal fattyacid elongation, an important pathway for saturated (SFA), mono- (MUFA) and polyunsaturated fattyacid (PUFA) synthesis. Despite the interest in ACC as a target for obesity and cancer therapy, little attention has been given to the role ACC plays in long chain fattyacid synthesis. This report examines the effect of pharmacological inhibition of ACC on DNL & palmitate (16:0) and linoleate (18:2,n-6) metabolism in HepG2 and LnCap cells. The ACC inhibitor, soraphen A, lowers cellular malonyl CoA, attenuates DNL and the formation of fattyacid elongation products derived from exogenous fattyacids, i.e., 16:0 & 18:2,n-6; IC50 ~ 5 nM. Elevated expression of fattyacid elongases (Elovl5, Elovl6) or desaturases (FADS1, FADS2) failed to override the soraphen A effect on SFA, MUFA or PUFA synthesis. Inhibition of fattyacid elongation leads to the accumulation of 16- and 18-carbon unsaturated fattyacids derived from 16:0 and 18:2,n-6, respectively. Pharmacological inhibition of ACC activity will not only attenuate DNL and induce FAO, but will also attenuate the synthesis of very long chain saturated, mono- and polyunsaturated fattyacids. PMID:21184748

Summary Very long chain fattyacids confer functional diversity on cells by variations in their chain length and degree of unsaturation. Microsomal fattyacid elongation represents the major pathway for determining the chain length of saturated, monounsaturated, and polyunsaturated fattyacids in cellular lipids. The overall reaction for fattyacid elongation involves four enzymes and utilizes malonyl CoA, NADPH, and fatty acyl CoA as substrates. While the fundamental pathway and its requirements have been known for many years, recent advances have revealed a family of enzymes involved in the first step of the reaction, i.e., the condensation reaction. Seven fattyacid elongase subtypes (Elovl #1–7) have been identified in the mouse, rat, and human genomes. These enzymes determine the rate of overall fattyacid elongation. Moreover, these enzymes also display differential substrate specificity, tissue distribution, and regulation, making them important regulators of cellular lipid composition as well as specific cellular functions. Herein, methods are described to measure elongase activity, analyze elongation products, and alter cellular elongase expression. PMID:19763486

Human skin fattyacids are a potent aspect of our innate defenses, giving surface protection against potentially invasive organisms. They provide an important parameter in determining the ecology of the skin microflora, and alterations can lead to increased colonization by pathogens such as Staphylococcus aureus. Harnessing skin fattyacids may also give a new avenue of exploration in the generation of control measures against drug-resistant organisms. Despite their importance, the mechanism(s) whereby skin fattyacids kill bacteria has remained largely elusive. Here, we describe an analysis of the bactericidal effects of the major human skin fattyacid cis-6-hexadecenoic acid (C6H) on the human commensal and pathogen S. aureus. Several C6H concentration-dependent mechanisms were found. At high concentrations, C6H swiftly kills cells associated with a general loss of membrane integrity. However, C6H still kills at lower concentrations, acting through disruption of the proton motive force, an increase in membrane fluidity, and its effects on electron transfer. The design of analogues with altered bactericidal effects has begun to determine the structural constraints on activity and paves the way for the rational design of new antistaphylococcal agents. PMID:24709265

Fattyacid (FA) transport and activation have been extensively studied in the model yeast species Saccharomyces cerevisiae but have rarely been examined in oleaginous yeasts, such as Yarrowia lipolytica. Because the latter begins to be used in biodiesel production, understanding its FA transport and activation mechanisms is essential. We found that Y. lipolytica has FA transport and activation proteins similar to those of S. cerevisiae (Faa1p, Pxa1p, Pxa2p, Ant1p) but mechanism of FA peroxisomal transport and activation differs greatly with that of S. cerevisiae. While the ScPxa1p/ScPxa2p heterodimer is essential for growth on long-chain FAs, ΔYlpxa1 ΔYlpxa2 is not impaired for growth on FAs. Meanwhile, ScAnt1p and YlAnt1p are both essential for yeast growth on medium-chain FAs, suggesting they function similarly. Interestingly, we found that the ΔYlpxa1 ΔYlpxa2 ΔYlant1 mutant was unable to grow on short-, medium-, or long-chain FAs, suggesting that YlPxa1p, YlPxa2p, and YlAnt1p belong to two different FA degradation pathways. We also found that YlFaa1p is involved in FA storage in lipid bodies and that FA remobilization largely depended on YlFat1p, YlPxa1p and YlPxa2p. This study is the first to comprehensively examine FA intracellular transport and activation in oleaginous yeast. PMID:25887939

Introduction. Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fattyacid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fattyacid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fattyacid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fattyacids of HDL. Conclusion. The fattyacid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fattyacids may improve the activity of PON1 and thereby have beneficial effects on health. PMID:24167374

This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fattyacids in transgenic plants. In addition, the use of genes encoding fattyacid hydroxylases or desaturases to alter the level of lipid fattyacid unsaturation in transgenic plants is described.

Fattyacid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fattyacids in cancer is unknown. It has been suggested that endogenous fattyacid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fattyacids synthesized endogenously from {sup 14}C-labeled acetate to those supplied exogenously as {sup 14}C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fattyacids that are different from those derived from exogenous palmitate, that these fattyacids are esterified to the same lipid and phospholipid classes in the same proportions, and that their distribution within neutral lipids is not different from untransformed cells. These results suggest that endogenously synthesized fattyacids do not fulfill a specific function in cancer cells. Furthermore, we observed that cancer cells excrete endogenously synthesized fattyacids, suggesting that they are produced in excess of requirements. We next investigated whether lipogenic activity is involved in the maintenance of high glycolytic activity by culturing both cancer and non-transformed cells under anoxic conditions. Although anoxia increased glycolysis 2–3 fold, we observed no concomitant increase in lipogenesis. Our results indicate that breast cancer cells do not have a specific qualitative or quantitative requirement for endogenously synthesized fattyacids and that increased de novo lipogenesis is not required to sustain elevations in glycolytic activity induced by anoxia in these cells. - Highlights: • Fattyacid synthase (FASN) is over-expressed in cancer but its function is unknown. • We compare

The dysfunction of ABCD1, a peroxisomal ABC protein, leads to the perturbation of very long chain fattyacid (VLCFA) metabolism and is the cause of X-linked adrenoleukodystrophy. Abcd1-deficient mice exhibit an accumulation of saturated VLCFAs, such as C26:0, in all tissues, especially the brain. The present study sought to measure microsomal fattyacid elongation activity in the brain of wild-type (WT) and abcd1-deficient mice during the course of development. The fattyacid elongation activity in the microsomal fraction was measured by the incorporation of [2-(14)C]malonyl-CoA into fattyacids in the presence of C16:0-CoA or C20:0-CoA. Cytosolic fattyacid synthesis activity was completely inhibited by the addition of N-ethylmaleimide (NEM). The microsomal fattyacid elongation activity in the brain was significantly high at 3 weeks after birth and decreased substantially at 3 months after birth. Furthermore, we detected two different types of microsomal fattyacid elongation activity by using C16:0-CoA or C20:0-CoA as the substrate and found the activity toward C20:0-CoA in abcd1-deficient mice was higher than the WT 3-week-old animals. These results suggest that during the active myelination phase the microsomal fattyacid elongation activity is stimulated in abcd1-deficient mice, which in turn perturbs the lipid composition in myelin. PMID:26108493

Omega-3 fattyacids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount ... the blood in people with very high triglycerides. Omega-3 fattyacids are in a class of medications ...

Omega-6 fattyacids are types of fats. Some types are found in vegetable oils, including corn, evening primrose seed, safflower, and soybean oils. Other types of omega-6 fattyacids are found in black currant seed, borage seed, ...

In one aspect, a radioactively labeled analog of a fattyacid which is capable of being taken up by mammalian tissue and which exhibits an in vivo beta-oxidation rate below that with a corresponding radioactively labeled fattyacid.

The present study investigated the effects of nutritional omega-3 polyunsaturated fattyacids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fattyacids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fattyacid-enriched food, the animals on the omega-3 fattyacid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fattyacids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fattyacids may play a role in the pathophysiology of ADHD. PMID:24415401

For making use of Ginseng resources and finding new anti-tumor drugs, the anti-tumor activity of three kinds of new panaxadiol fattyacid ester derivates: 3beta-acetoxy panaxadiol (I), 3beta-palmitic acid aceloxy panaxadiol (II), 3beta-octadecanoic acid aceloxy panaxadiol (Ill) and panaxaiol were compared through the method of cell stain and counting. Tumor cell was Vero cell line. Positive control was 5-FU. Blank was RPM11640 culture medium. Negative control was RPM11640 culture medium and the solvent for subjected drugs. The result showed that compound I had the strongest anti-tumor activity, second was panaxadiol, II and III had the same and the weakest antitumor activity. Furthermore, the anti-tumor activities of panaxadiol fattyacid ester derivates showed positive correlation with subjects' concentrations, but no relationship with molecular weight of fattyacid. PMID:17228662

The biochemical response to controlled inhalation of nitrogen dioxide (NO2) was studied in 18 male guinea pigs. Animals were exposed to 2.5, 5.0, and 10 ppm NO2 for 2h daily for 35 consecutive days, and the results compared with six control animals exposed to filtered air for 2h daily for same period. Five biochemical parameters, including triglyceride, free fattyacids, esterified fattyacid, ganglioside and lipase activity were measured immediately after the last day of exposure. At 2.5 ppm NO2 inhalation no significant changes occurred in any region of the central nervous system (CNS). While as the dose concentration was increased to 5 and 10 ppm nitrogen dioxide, significant dose-related alteration were observed in the levels of triglyceride, free fattyacid, esterified fattyacid, ganglioside and lipase activity in the different regions of the guinea pig CNS.

Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fattyacids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report (ATVB 11:1944, 2009) suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for conjugating f...

Epicuticular wax production was evaluated along the length of expanding leek (Allium porrum L.) leaves to gain insight into the regulation of wax production. Leaf segments from the bottom to the top were analyzed for (a) wax composition and load; (b) microsomal fattyacid elongase, plastidial fattyacid synthase, and acyl-acyl carrier protein (ACP) thioesterase activities; and (c) tissue and cellular morphological changes. The level of total wax, which was low at the bottom, increased 23-fold along the length of the leaf, whereas accumulation of the hentriacontan-16-one increased more than 1000-fold. The onset of wax accumulation was not linked to cell elongation but, rather, occurred several centimeters above the leaf base. Peak microsomal fattyacid elongation activity preceded the onset of wax accumulation, and the maximum fattyacid synthase activity was coincident with the onset. The C16:0- and C18:0-ACP-hydrolyzing activities changed relatively little along the leaf, whereas C18:1-ACP-hydrolyzing activity increased slightly prior to the peak elongase activity. Electron micrographic analyses revealed that wax crystal formation was asynchronous among cells in the initial stages of wax deposition, and morphological changes in the cuticle and cell wall preceded the appearance of wax crystals. These studies demonstrated that wax production and microsomal fattyacid elongation activities were induced within a defined and identifiable region of the expanding leek leaf and provide the foundation for future molecular studies. PMID:9501123

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fattyacids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fattyacids have a dual role in various human and murine models. In contrast, polyunsaturated fattyacids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fattyacids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fattyacids possible biomarkers for NAFLD. Bioactive fattyacids provide health benefits through modification of fattyacid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fattyacids in nutritional and clinical treatment strategies for patients with NAFLD. PMID:27485440

Phospholipids are well known for their membrane-forming properties and thereby delimit any cell from the exterior world. In addition, membrane phospholipids can act as precursors for signals and other biomolecules during their turnover. Little is known about phospholipid signalling, turnover and remodelling in bacteria. Recently, we showed that a FadD-deficient mutant of Sinorhizobium meliloti, unable to convert free fattyacids to their coenzyme A derivatives, accumulates free fattyacids during the stationary phase of growth. Enzymatic activities responsible for the generation of these free fattyacids were unknown in rhizobia. Searching the genome of S. meliloti, we identified a potential lysophospholipase (SMc04041) and two predicted patatin-like phospholipases A (SMc00930, SMc01003). Although SMc00930 as well as SMc01003 contribute to the release of free fattyacids in S. meliloti, neither one can use phospholipids as substrates. Here we show that SMc01003 converts diacylglycerol to monoacylglycerol and a fattyacid, and that monoacylglycerol can be further degraded by SMc01003 to another fattyacid and glycerol. A SMc01003-deficient mutant of S. meliloti transiently accumulates diacylglycerol, suggesting that SMc01003 also acts as diacylglycerol lipase (DglA) in its native background. Expression of the DglA lipase in Escherichia coli causes lysis of cells in stationary phase of growth. PMID:25711932

Peroxisome proliferators (PPs) are potent tumor promoters in rodents. The mechanism of hepatocarcinogenesis requires the nuclear receptor peroxisome proliferator activated receptor-alpha (PPARalpha), but might also involve the PPARalpha independent alteration of signaling pathways that regulate cell growth. Here, we studied the effects of PPs on the mevalonate pathway, a critical pathway that controls cell proliferation. Liver X receptors (LXRs) are nuclear receptors that act as sterol sensors in the mevalonate pathway. In gene reporter assays in COS-7 cells, the basal activity of the LXR responsive reporter gene (LXRE-luc) was suppressed by 10 microM lovastatin and zaragozic acid A, suggesting that this activity was attributed to the activation of native LXRs, by endogenously produced mevalonate products. The potent PP and rodent tumor promoter, pirinixic acid (WY-14643) also inhibited LXR-mediated transcription in a dose related manner (approximate IC(50) of 100 microM). As did several other PPs including ciprofibric acid and mono-ethylhexylphthalate. Polyunsaturated and medium to long chain fattyacids at 100 microM were also potent inhibitors; the arachidonic acid analogue eicosatetraynoic acid being the most active (approximate IC(50) of 10 microM). Of the PPs and fattyacids tested, there was a strong correlation between the ability of these agents to suppress de novo sterol synthesis in a rat hepatoma cell line, H4IIEC3, and inhibit LXR-mediated transcription in COS-7 cells, but a discordance between these endpoints and PPARalpha activation and fattyacid acyl-CoA oxidase induction. Taken together, these results suggest that PPs and fattyacids negatively regulate the mevalonate pathway through a mechanism that is not entirely dependent on PPARalpha activation. Because of the importance of the mevalonate pathway in regulating cell proliferation, the modulation of this pathway by PPs and fattyacids might contribute to their actions on cell growth

Antibacterial activity of alkaline salts of caproic, caprylic, capric, lauric, and myristic acids were determined using the agar diffusion assay. A 0.5M concentration of each fattyacid (FA) was dissolved in 1.0 M potassium hydroxide (KOH), and pH of the mixtures was adjusted to 10.5 with citric aci...

Decarboxylation of fattyacids over non-noble metal catalysts without added hydrogen was studied. Ni/C catalysts were prepared and exhibited excellent activity and maintenance for decarboxylation. Thereafter, the effects of nickel loading, catalyst loading, temperature, and carbon number on the decarboxylation of fattyacids were investigated. The results indicate that the products of cracking increased with high nickel loading or catalyst loading. Temperature significantly impacted the conversion of stearic acid but did not influence the selectivity. The fattyacids with large carbon numbers tend to be cracked in this reaction system. Stearic acid can be completely converted at 370 °C for 5 h, and the selectivity to heptadecane was around 80%.

Decarboxylation of fattyacids over non-noble metal catalysts without added hydrogen was studied. Ni/C catalysts were prepared and exhibited excellent activity and maintenance for decarboxylation. Thereafter, the effects of nickel loading, catalyst loading, temperature, and carbon number on the decarboxylation of fattyacids were investigated. The results indicate that the products of cracking increased with high nickel loading or catalyst loading. Temperature significantly impacted the conversion of stearic acid but did not influence the selectivity. The fattyacids with large carbon numbers tend to be cracked in this reaction system. Stearic acid can be completely converted at 370 °C for 5 h, and the selectivity to heptadecane was around 80%. PMID:27292280

Decarboxylation of fattyacids over non-noble metal catalysts without added hydrogen was studied. Ni/C catalysts were prepared and exhibited excellent activity and maintenance for decarboxylation. Thereafter, the effects of nickel loading, catalyst loading, temperature, and carbon number on the decarboxylation of fattyacids were investigated. The results indicate that the products of cracking increased with high nickel loading or catalyst loading. Temperature significantly impacted the conversion of stearic acid but did not influence the selectivity. The fattyacids with large carbon numbers tend to be cracked in this reaction system. Stearic acid can be completely converted at 370 °C for 5 h, and the selectivity to heptadecane was around 80%. PMID:27292280

A complex formed by human α-lactalbumin (α-LA) and oleic acid (OA), named HAMLET, has been shown to have an apoptotic activity leading to the selective death of tumor cells. In numerous publications it has been reported that in the complex α-LA is monomeric and adopts a partly folded or "molten globule" state, leading to the idea that partly folded proteins can have "beneficial effects". The protein/OA molar ratio initially has been reported to be 1:1, while recent data have indicated that the OA-complex is given by an oligomeric protein capable of binding numerous OA molecules per protein monomer. Proteolytic fragments of α-LA, as well as other proteins unrelated to α-LA, can form OA-complexes with biological activities similar to those of HAMLET, thus indicating that a generic protein can form a cytotoxic complex under suitable experimental conditions. Moreover, even the selective tumoricidal activity of HAMLET-like complexes has been questioned. There is recent evidence that the biological activity of long chain unsaturated fattyacids, including OA, can be ascribed to their effect of perturbing the structure of biological membranes and consequently the function of membrane-bound proteins. In general, it has been observed that the cytotoxic effects exerted by HAMLET-like complexes are similar to those reported for OA alone. Overall, these findings can be interpreted by considering that the protein moiety does not have a toxic effect on its own, but merely acts as a solubilising agent for the inherently toxic fattyacid. PMID:23499846

Greater amounts of physical activity (PA) and omega-3 fattyacids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fattyacids and PA, fattyacid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fattyacid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age = 44.42 years, SD = 6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fattyacid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fattyacid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fattyacids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health. PMID:24813150

Greater amounts of physical activity (PA) and omega-3 fattyacids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fattyacids and PA, fattyacid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fattyacid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age=44.42 years, SD=6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fattyacid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fattyacid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fattyacids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health. PMID:24813150

Since the first fattyacid amino acid conjugate (FAC) was isolated from regurgitant of Spodoptera exigua larvae in 1997 [volicitin: N-(17-hydroxylinolenoyl)- L-glutamine], their role as elicitors of induced responses in plants has been well documented. However, studies of the biosyntheses as well as...

The fruits of eight myrtles, Myrtus communis L. accessions from the Mediterranean region of Turkey were evaluated for their antioxidant activities and fattyacid contents. The antioxidant activities of the fruit extracts were determined by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene-linoleic acid assays. The fattyacid contents of fruits were determined by using gas chromatography. The methanol extracts of fruits exhibited a high level of free radical scavenging activity. There was a wide range (74.51-91.65%) of antioxidant activity among the accessions in the β-carotene-linoleic acid assay. The amount of total phenolics (TP) was determined to be between 44.41-74.44 μg Gallic acid equivalent (GAE)/mg, on a dry weight basis. Oleic acid was the dominant fattyacid (67.07%), followed by palmitic (10.24%), and stearic acid (8.19%), respectively. These results suggest the future utilization of myrtle fruit extracts as food additives or in chemoprevention studies. PMID:20548930

The absolute fat requirement of the human species is the amount of essential fattyacids needed to maintain optimal fattyacid composition of all tissues and normal eicosanoid synthesis. At most, this requirement is no more than about 5% of an adequate energy intake. However, fat accounts for appro...

Omega-3 fattyacids are used together with lifestyle changes (diet, weight-loss, exercise) to reduce the amount of triglycerides (a fat-like ... people with very high triglycerides. Omega-3 fattyacids are in a class of medications called antilipemic ...

We have conducted an investigation designed to identify alternate catalysts for the production of fattyacid methyl esters (FAME) to be used as biodiesel. Diphenylammonium sulfate (DPAS) and diphenylammonium chloride (DPA-HCl) salts were found to be highly active homogeneous catalysts for the simu...

Diphenylamine sulfate (DPAS) and diphenylamine hydrochloride (DPACl) salts were found to be highly active catalysts for esterification and transesterification of inexpensive greases to fattyacid methyl esters (FAME). In the presence of catalytic amounts of DPAS or DPACl and excess methanol, the fr...

The metabolically inert perfluorinated fattyacids perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) can display fattyacid-like activity in biological systems. The uncoupling protein 1 (UCP1) in brown adipose tissue is physiologically (re)activated by fattyacids, including octanoate. This leads to bioenergetically uncoupled energy dissipation (heat production, thermogenesis). We have examined here the possibility that PFOA/PFOS can directly (re)activate UCP1 in isolated mouse brown-fat mitochondria. In wild-type brown-fat mitochondria, PFOS and PFOA overcame GDP-inhibited thermogenesis, leading to increased oxygen consumption and dissipated membrane potential. The absence of this effect in brown-fat mitochondria from UCP1-ablated mice indicated that it occurred through activation of UCP1. A competitive type of inhibition by increased GDP concentrations indicated interaction with the same mechanistic site as that utilized by fattyacids. No effect was observed in heart mitochondria, i.e., in mitochondria without UCP1. The stimulatory effect of PFOA/PFOS was not secondary to non-specific mitochondrial membrane permeabilization or to ROS production. Thus, metabolic effects of perfluorinated fattyacids could include direct brown adipose tissue (UCP1) activation. The possibility that this may lead to unwarranted extra heat production and thus extra utilization of food resources, leading to decreased fitness in mammalian wildlife, is discussed, as well as possible negative effects in humans. However, a possibility to utilize PFOA-/PFOS-like substances for activating UCP1 therapeutically in obesity-prone humans may also be envisaged. PMID:26041126

Hydroxy fattyacids have gained industrial attention because of their special properties such as higher viscosity and reactivity compared with other non-hydroxy fattyacids. The bacterial isolate Pseudomonas aeruginosa (PR3) had been reported to produce mono-, di-, and tri-hydroxy fattyacids from ...

Hydroxy fattyacids (HFA) have gained important attentions because of their special properties such as higher viscosity and reactivity compared with other non-hydroxy fattyacids. Pseudomonas aeruginosa (PR3) had been reported to produce mono-, di-, and tri-hydroxy fattyacids from different unsatu...

In this study we evaluated the biting deterrent effects of a series of saturated and unsaturated fattyacids against Aedes aegypti (L), yellow fever mosquito (Diptera: Culicidae) using the K & Dbioassay module system. Saturated (C6:0 to C16:0 and C18:0) and unsaturated fattyacids (C11:1 to C14:1, C16:1, C18:1, and C18:2) showed biting deterrence index (BDI) values significantly greater than ethanol, the negative control. Among the saturated fattyacids, mid chain length acids (C10:0 to C13:0) showed higher biting deterrence than short (C6:0 to C9:0) and long chain length acids (C14:0 to C18:0), except for C8:0 and C16:0 that were more active than the other short and long chain acids. The BDI values of mid chain length acids (C10:0 to C13:0) were not significantly less than N, N-diethyl-meta-toluamide (DEET), the positive control. Among the unsaturated fattyacids, C11:1 showed the highest activity (BDI = 1.05) and C18:2 had the lowest activity (BDI = 0.7). In C11:1, C12:1, and C14:1 BDI values were not significantly less than DEET. After the preliminary observations, residual activity bioassays were performed on C11:0, C12:0, C11:1, and C12:1 over a 24-h period. All the fattyacids (C11:0, C12:0, C11:1, and C12:1) and DEET showed significantly higher activity at all test intervals than the solvent control. At treatment and 1-h posttreatment, all fattyacids showed proportion not biting (PNB) values not significantly less than DEET. At 3-, 6-, and 12-h posttreatment, all fattyacids showed PNB values significantly greater than DEET. At 24-h posttreatment, only the PNB value for C12:0 was significantly higher than DEET. The dose-responses of C12:0 and DEET were determined at concentrations of 5-25 nmol/cm2. As in the residual activity bioassays, the PNB values for C12:0 and DEET at 25 nmol/cm(2) were not significantly different. However, at lower concentrations, the PNB values for C12:0 were significantly greater than DEET. These results clearly indicate that mid

The formation of 14C-labelled long-chain and very-long-chain (n-3) pentaenoic and hexaenoic fattyacids was studied in bovine retina by following the metabolism of. [14C]-docosapentaenoate [C22:5, n-3 fattyacid (22:5 n-3)], [14C]-docosahexaenoate (22:6 n-3), and [14C]acetate. With similar amounts of 22:5 n-3 and 22:6 n-3 as substrates, the former was actively transformed into 24:5 n-3, whereas the latter was virtually unmodified. Labelled 24:5, 26:5, 24:6 and 22:6 were formed from [1-14C]22:5 n-3, showing that pentaenoic fattyacids including 24:5 n-3 can be elongated and desaturated within the retina. When retinal microsomes were incubated with [1-14C]22:5 n-3, 24:5 n-3 was the only fattyacid formed. In retinas incubated with [14C]acetate, 24:5 n-3 was the most highly labelled fattyacid among the polyenes synthesized, 24:6 n-3 being a minor product. Such selectivity in the elongation of two fattyacids identical in length, 22:5 n-3 and 22:6 n-3, despite the fact that 22:5 is a minor and 22:6 a major fattyacid constituent of retina, suggests that the active formation of 24:5 n-3 plays a key role in n-3 polyunsaturated fattyacid (PUFA) metabolism. This compound might give rise to even longer pentaenes via elongation, and to the major PUFAs of retina, 22:6 n-3, by 6-desaturation and chain shortening. Of all retinal lipids, a minor component, triacylglycerol (TG), incorporated the largest amounts of [14C]22:5 and 22:6. TG also concentrated most of the [14C]24:5 formed in retina, whether from [14C]22:5 n-3 or from [14C]acetate, suggesting an important role for this lipid in supporting PUFA metabolism and the synthesis of 22:6 n-3. PMID:8670163

Background Fattyacid modifying enzyme (FAME) has been shown to modify free fattyacids to alleviate their bactericidal effect by esterifying fattyacids to cholesterol or alcohols. Although it has been shown in previous studies that FAME is required for Staphylococcus aureus survival in skin abscesses, FAME is poorly studied compared to other virulence factors. FAME activity had also been detected in coagulase-negative staphylococci (CNS). However, FAME activity was only surveyed after a bacterial culture was grown for 24 h. Therefore if FAME activity was earlier in the growth phase, it would not have been detected by the assay and those strains would have been labeled as FAME negative. Results Fifty CNS bovine mastitis isolates and several S. aureus, Escherichia coli, and Streptococcus uberis strains were assayed for FAME activity over 24 h. FAME activity was detected in 54% of CNS and 80% S. aureus strains surveyed but none in E. coli or S. uberis. While some CNS strains produced FAME activity comparable to the lab strain of S. aureus, the pattern of FAME activity varied among strains and across species of staphylococci. All CNS that produced FAME activity also exhibited lipase activity. Lipase activity relative to colony forming units of these CNS decreased over the 24 h growth period. No relationship was observed between somatic cell count in the milk and FAME activity in CNS. Conclusions Some staphylococcal species surveyed produced FAME activity, but E. coli and S. uberis strains did not. All FAME producing CNS exhibited lipase activity which may indicate that both these enzymes work in concert to alter fattyacids in the bacterial environment. PMID:22726316

Fats and their various fattyacid components seem to be a perennial concern of nutritionists and persons concerned with healthful diets. Advice on the consumption of saturated, polyunsaturated, monounsaturated, and total fat bombards us from magazines and newspapers. One of the newer players in this field is the group of trans fattyacids found predominantly in partially hydrogenated fats such as margarines and cooking fats. The controversy concerning dietary trans fattyacids was recently addressed in an American Heart Association (AHA) science advisory (1) and in a position paper from the American Society of Clinical Nutrition/American Institute of Nutrition (ASCN/AIN) (2). Both reports emphasize that the best preventive strategy for reducing risk for cardiovascular disease and some types of cancer is a reduction in total and saturated fats in the diet, but a reduction in the intake of trans fattyacids was also recommended. Although the actual health effects of trans fattyacids remain uncertain, experimental evidence indicates that consumption of trans fattyacids adversely affects serum lipid levels. Since elevated levels of serum cholesterol and triacylglycerols are associated with increased risk of cardiovascular disease, it follows that intake of trans fattyacids should be minimized.

A series of novel l-ascorbyl fattyacid esters were synthesized by catalization of Novozym(®) 435 under ultrasonic irradiation and characterized by infrared spectroscopy, electrospray ionization mass spectra, and nuclear magnetic resonance. Their properties especially antioxidant activity and stability were investigated. The results showed that the reducing power, the scavenging activity of hydroxyl radical and 2,2-diphenyl-1-picrylhydrazyl radical were decreased with the increase of the number of carbon atoms in fattyacid. The hydroxyl radical scavenging activity and reducing power of l-ascorbyl saturated fattyacid esters were better than that of tert-butylhydroquinone. The induction period in lipid oxidation of l-ascorbyl saturated fattyacid esters and tert-butylhydroquinone were longer than that of l-ascorbyl unsaturated fattyacid esters and l-ascorbic acid both in soybean oil and lard. Besides, the l-ascorbyl fattyacid esters showed different stabilities in different conditions by comparing with l-ascorbic acid, and the l-ascorbyl saturated fattyacid esters were more stable than l-ascorbyl unsaturated fattyacid esters in ethanol solution. PMID:27100741

Objective This study is to assess the antibacterial activity of omega-6, -7, -9 (n-6, n-7, n-9) fattyacids against various oral microorganisms. Methods The n-6, n-7, n-9 fattyacids, such as γ-linoleic acid (GLA), linoleic acid (LA), arachidonic acid (ARA), palmitoleic acid (PA), and oleic acid (OA), their fattyacid ethyl esters, GLA-EE, LA-EE, ARA-EE, PA-EE, OA-EE, and their fattyacid methyl esters, GLA-ME, LA-ME, ARA-ME, PA-ME, OA-ME were investigated for antimicrobial activity against oral pathogens Streptococcus mutans, Candida albicans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis. Various concentrations of the fattyacids, their methyl and ethyl esters were tested against various oral pathogens in 96-well plates and blood-agar plate. The plates were incubated anaerobically or aerobically at 37°C for 48 hours, and the colony forming units (CFU) were determined. Results The data demonstrated that select n-6, n-7, n-9 fattyacids and their esters exhibited strong antimicrobial activity against these oral microorganisms, demonstrating some specificity for individual microbial species. Conclusion The potential use or the combinations of the n-6, n-7, n-9 fattyacids and/or their esters, provided in a local delivery vehicle to infected sites in the oral cavity, could be considered as an additional therapeutic approach to improving oral health. PMID:20541177

Fattyacids are essential components of the dynamic lipid metabolism in cells. Fattyacids can also signal to intracellular pathways to trigger a broad range of cellular responses. Oleic acid is an abundant monounsaturated omega-9 fattyacid that impinges on different biological processes, but the mechanisms of action are not completely understood. Here, we report that oleic acid stimulates the cAMP/protein kinase A pathway and activates the SIRT1-PGC1α transcriptional complex to modulate rates of fattyacid oxidation. In skeletal muscle cells, oleic acid treatment increased intracellular levels of cyclic adenosine monophosphate (cAMP) that turned on protein kinase A activity. This resulted in SIRT1 phosphorylation at Ser-434 and elevation of its catalytic deacetylase activity. A direct SIRT1 substrate is the transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α), which became deacetylated and hyperactive after oleic acid treatment. Importantly, oleic acid, but not other long chain fattyacids such as palmitate, increased the expression of genes linked to fattyacid oxidation pathway in a SIRT1-PGC1α-dependent mechanism. As a result, oleic acid potently accelerated rates of complete fattyacid oxidation in skeletal muscle cells. These results illustrate how a single long chain fattyacid specifically controls lipid oxidation through a signaling/transcriptional pathway. Pharmacological manipulation of this lipid signaling pathway might provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation. PMID:23329830

This study reports in vitro anticholinesterase, antioxidant and antimicrobial effects of the n-hexane, dichloromethane, ethanol and ethanol-water extracts prepared from Pistacia terebinthus L. fruits and Pistacia khinjuk Stocks seeds as well as their total phenolic and flavonoid contents, and fattyacid compositions. Ethanol and ethanol-water extracts of both species exhibited higher anticholinesterase activity than galanthamine. Among ABTS, DPPH and CUPRAC assays, the highest antioxidant capacity of the extracts was found in the last one. P. terebinthus ethanol extract being rich in flavonoid content showed the best cupric reducing effect. All extracts possessed no antimicrobial activity. The main fattyacid in P. terebinthus fruits (52.52%) and P. khinjuk seeds (59.44%) was found to be oleic acid. Our results indicate that P. terebinthus fruits and P. khinjuk seeds could be a good source of anticholinesterase compounds, and could be phytochemically investigated. PMID:25115646

Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a novel target for antibacterial drug development. In the screening of inhibitors of Staphylococcus aureus enoyl-ACP reductase (FabI), complestatin was isolated as a potent inhibitor of S. aureus FabI together with neuroprotectin A and chloropeptin I from Streptomyces chartreusis AN1542. Complestatin and related compounds inhibited S. aureus FabI with IC₅₀ of 0.3-0.6 µM. They also prevented the growth of S. aureus as well as methicillin-resistance S. aureus (MRSA) and quinolone-resistant S. aureus (QRSA), with minimum inhibitory concentrations (MICs) of 2-4 µg/mL. Consistent with its FabI-inhibition, complestatin selectively inhibited the intracellular fattyacid synthesis in S. aureus, whereas it did not affect the macromolecular biosynthesis of other cellular components, such as DNA, RNA, proteins, and the cell wall. Additionally, supplementation with exogenous fattyacids reversed the antibacterial effect of complestatin, demonstrating that it targets fattyacid synthesis. In this study, we reported that complestatin and related compounds showed potent antibacterial activity via inhibiting fattyacid synthesis. PMID:25947917

The formation of fattyacids by Fischer-Tropsch-type synthesis was investigated with ferric oxide, ammonium carbonate, potassium carbonate, powdered Pueblito de Allende carbonaceous chondrite, and filings from the Canyon Diablo meteorite used as catalysts. Products were separated and identified by gas chromatography and mass spectrometry. Iron oxide, Pueblito de Allende chondrite, and Canyon Diablo filings in an oxidized catalyst form yielded no fattyacids. Canyon Diablo filings heated overnight at 500 C while undergoing slow purging by deuterium produced fattyacids only when potassium carbonate was admixed; potassium carbonate alone also produced these compounds. The active catalytic combinations gave relatively high yields of aliphatic and aromatic hydrocarbons; substantial amounts of n-alkenes were almost invariably observed when fattyacids were produced; the latter were in the range C6 to C18, with maximum yield in C9 or 10.

Arabidopsis thaliana seed maturation is accompanied by the deposition of storage oil, rich in the essential ω-3 polyunsaturated fattyacid α-linolenic acid (ALA). The synthesis of ALA is highly responsive to the level of FATTYACID DESATURASE3 (FAD3) expression, which is strongly upregulated during embryogenesis. By screening mutants in LEAFY COTYLEDON1 (LEC1)–inducible transcription factors using fattyacid profiling, we identified two mutants (lec1-like and bzip67) with a seed lipid phenotype. Both mutants share a substantial reduction in seed ALA content. Using a combination of in vivo and in vitro assays, we show that bZIP67 binds G-boxes in the FAD3 promoter and enhances FAD3 expression but that activation is conditional on bZIP67 association with LEC1-LIKE (L1L) and NUCLEAR FACTOR-YC2 (NF-YC2). Although FUSCA3 and ABSCISIC ACID INSENSITIVE3 are required for L1L and bZIP67 expression, neither protein is necessary for [bZIP67:L1L:NF-YC2] to activate FAD3. We conclude that a transcriptional complex containing L1L, NF-YC2, and bZIP67 is induced by LEC1 during embryogenesis and specifies high levels of ALA production for storage oil by activating FAD3 expression. PMID:23995083

Ten subjects (from 27 to 41 years) have been participated in 32 experiments. They were decompressed from ground level to 40-35 kPa in altitude chamber when breathed 100% oxygen by mask and performed repeated cycles of exercises (3.0 Kcal/min). The intervals between decompressions were 3-5 days. Plasma lipid and erythrocyte membrane fattyacid composition was evaluated in the fasting venous blood before and immediately after hypobaric exposure. There were 7 cases decompression sickness (DCS). Venous gas bubbles (GB) were detected in 27 cases (84.4%). Any significant changes in the fattyacid composition of erythrocyte membranes and plasma didn't practically induce after the first decompression. However, by the beginning of the second decompression the total lipid level in erythrocyte membranes decreased from 54.6 mg% to 40.4 mg% in group with DCS symptoms and from 51.2 mg% to 35.2 mg% (p < 0.05) without DCS symptoms. In group with DCS symptoms a tendency to increased level of saturated fattyacids in erythrocyte membranes (16:0, 18:0), the level of the polyunsaturated linoleic fattyacid (18:2) and arachidonic acid (20:4) tended to be decreased by the beginning of the second decompression. Insignificant changes in blood plasma fattyacid composition was observed in both groups. The obtained biochemical data that indicated the simulated extravehicular activity (EVA) condition is accompanied by the certain changes in the blood lipid metabolism, structural and functional state of erythrocyte membranes, which are reversible. The most pronounced changes are found in subjects with DCS symptoms.

Saturated fattyacids can activate Toll-like receptor 2 (TLR2) and TLR4 but polyunsaturated fattyacids, particularly docosahexaenoic acid (DHA) inhibit the activation. Lipopolysaccharides (LPS) and lipopetides, ligands for TLR4 and TLR2, respectively, are acylated by saturated fattyacids. Removal of these fattyacids results in loss of their ligand activity suggesting that the saturated fatty acyl moieties are required for the receptor activation. X-ray crystallographic studies revealed that these saturated fatty acyl groups of the ligands directly occupy hydrophobic lipid binding domains of the receptors (or co-receptor) and induce the dimerization which is prerequisite for the receptor activation. Saturated fattyacids also induce the dimerization and translocation of TLR4 and TLR2 into lipid rafts in plasma membrane and this process is inhibited by DHA. Whether saturated fattyacids induce the dimerization of the receptors by interacting with these lipid binding domains is not known. Many experimental results suggest that saturated fattyacids promote the formation of lipid rafts and recruitment of TLRs into lipid rafts leading to ligand independent dimerization of the receptors. Such a mode of ligand independent receptor activation defies the conventional concept of ligand induced receptor activation; however, this may enable diverse non-microbial molecules with endogenous and dietary origins to modulate TLR-mediated immune responses. Emerging experimental evidence reveals that TLRs play a key role in bridging diet-induced endocrine and metabolic changes to immune responses. PMID:27085899

High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance; yet, how IL-1β is induced by fattyacid with HFD, and how this alters insulin signaling is unclear. We show that the saturated fattyacid, palmitate, but not unsaturated oleate, induces the activation of NLRP3-PYCARD inflammasome, causing caspase-1, IL-1β, and IL-18 production. This involves mitochondrial reactive oxygen species and the AMP-activated protein kinase and ULK1 autophagy signaling cascade. Inflammasome activation in hematopoietic cells impairs insulin signaling in several target tissues to reduce glucose tolerance and insulin sensitivity. Furthermore, IL-1β affects insulin sensitivity via TNF-independent and dependent pathways. These findings provide insights into the association of inflammation, diet and T2D. PMID:21478880

In nephrotic syndrome, large quantities of albumin enter the kidney tubule. This albumin carries with it a heavy load of fattyacids to which the proximal tubule cells are exposed at high concentration. It is postulated that exposure to fattyacids in this way is injurious to proximal tubule cells. This study has examined the ability of fattyacids to interact with peroxisome proliferator-activated receptors (PPAR) in primary cultures of human proximal tubule cells. Luciferase reporter assays in transiently transfected human proximal tubule cells were used to show that albumin bound fattyacids and other agonists activate PPARgamma in a dose-dependent manner. One of the consequences of this activation is apoptosis of the cells as determined by changes in cell morphology, evidence of PARP cleavage, and appearance of DNA laddering. Overexpression of PPARgamma in these cells also results in enhanced apoptosis. Both fattyacid-induced PPAR activation and apoptosis in these cells can be blocked by PPAR response element decoy oligonucleotides. Activation of PPARgamma by the specific agonist PGJ(2) is associated with inhibition of cell proliferation, whereas activation by albumin bound fattyacids is accompanied by increased proliferation. However, the net balance of apoptosis/proliferation favors deletion of cells. These results implicate albumin-bound fattyacids as important mediators of tubular injury in nephrosis and provide fresh impetus for pursuit of lipid-lowering strategies in proteinuric renal disease. PMID:12506134

A multi-method active learning approach (MALA) was implemented in the Medical Biochemistry teaching unit of the Biomedical Sciences degree at the University of Aveiro, using problem-based learning as the main learning approach. In this type of learning strategy, students are involved beyond the mere exercise of being taught by listening. Less…

Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation. Expression of the fattyacid transporter CD36, another PPARgamma target, is also increased in Tg mice associated with elevated fattyacid uptake as measured in primary hepatocytes. Elevated expression of AMPK in the liver of Tg leads to phosphorylation of acetyl CoA carboxylase, indicating a decreased activity of the enzyme. Fattyacid synthase expression is also induced but the hepatic lipogenesis measured in vivo is not significantly different between WT and Tg mice. In addition, expression of carnitine palmitoyl transferase 1, the rate-limiting enzyme of beta-oxidation, is slightly upregulated. Finally, we show that overexpressing H-apoD in HepG2 cells in presence of arachidonic acid (AA), the main apoD ligand, increases the transcriptional activity of PPARγ. Supporting the role of apoD in AA transport, we observed enrichment in hepatic AA and a decrease in plasmatic AA concentration. Taken together, our results demonstrate that the hepatic steatosis observed in apoD Tg mice is a consequence of increased PPARγ transcriptional activity by AA leading to increased fattyacid uptake by the liver. PMID:26083030

It has been postulated that fattyacids found in edible oils may exert beneficial health effects by the modulation of signaling pathways regulating cell differentiation and proliferation, especially in the treatment of cardiovascular diseases. In the present study, the biological effects of selected edible oils--linseed (LO) and rapeseed (RO) oils--were tested in vitro on fibroblast cells. The fattyacid profile of the oils was determined using gas chromatography and FTIR spectroscopy. LO was found to be rich in α-linolenic acid (ALA), whereas oleic acid was the most abundant species in RO. Fattyacids were taken up by the cells and promoted cell proliferation. No oxidative stress-mediated cytotoxic or genotoxic effects were observed after oil stimulation. Oils ameliorated the process of wound healing as judged by improved migration of fibroblasts to the wounding area. As ALA-rich LO exhibited the most potent wound healing activity, ALA may be considered a candidate for promoting the observed effect. PMID:26703545

Imidazoline surfactants belong to the category of cationic surfactants. Cationic surfactants are often quaternary nitrogen salts and are widely used both in nonaqueous systems and in applications such as textile softeners, dispersants, and emulsifiers. This study describes the surface-active properties of cationic imidazolinium surfactants synthesized from different fattyacids. Their laundry performance in combination with nonionic surfactants like detergency, foaming property, softening property, rewettability etc., is also emphasized.

Probiotics are the class of beneficial microorganisms that have positive influence on the health when ingested in adequate amounts. Probiotic fermented milk is one of the dairy products that is prepared by using probiotic lactic acid bacteria. The study comprised preparation of fermented milk from various sources such as cow, goat and camel. Pediococcus pentosaceus which is a native laboratory isolate from cheese was utilized for the product formation. Changes in functional properties in the fermented milks obtained from three different species were evaluated. Antioxidant activity determined by DPPH assay showed activity in probiotic fermented milk obtained from all the products being highest in goat milk (93 %) followed by product from camel milk (86 %) and then product from cow milk (79 %). The composition of beneficial fattyacids such as stearic acid, oleic acid and linoleic acid were higher in fermented milk than the unfermented ones. Results suggested that probiotic bacteria are able to utilize the nutrients in goat and camel milk more efficiently compared to cow milk. Increase in antioxidant activity and fattyacid profile of fermented milks enhances the therapeutic value of the products. PMID:25477694

Pure volatile fattyacid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fattyacids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. PMID:27038264

The NLRP3 inflammasome is involved in many obesity-associated diseases, such as type 2 diabetes, atherosclerosis, and gouty arthritis, through its ability to induce interleukin (IL)-1β release. The molecular link between obesity and inflammasome activation is still unclear, but free fattyacids have been proposed as one triggering event. Here we reported opposite effects of saturated fattyacids (SFAs) compared with unsaturated fattyacids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers, including nigericin, alum, and monosodium urate. UFAs did not affect the transcriptional effect of SFAs, suggesting a specific effect on the NLRP3 activation. These results provide a new anti-inflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and, therefore, IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. PMID:24006511

Dietary fat was recognized as a good source of energy and fat-soluble vitamins by the first part of the 20th century, but fattyacids were not considered to be essential nutrients because they could be synthesized from dietary carbohydrate. This well-established view was challenged in 1929 by George and Mildred Burr who reported that dietary fattyacid was required to prevent a deficiency disease that occurred in rats fed a fat-free diet. They concluded that fattyacids were essential nutrients and showed that linoleic acid prevented the disease and is an essential fattyacid. The Burrs surmised that other unsaturated fattyacids were essential and subsequently demonstrated that linolenic acid, the omega-3 fattyacid analog of linoleic acid, is also an essential fattyacid. The discovery of essential fattyacids was a paradigm-changing finding, and it is now considered to be one of the landmark discoveries in lipid research. PMID:25339684

In this study we systematically evaluated for the first time the biting deterrent effects of a series of saturated and unsaturated fattyacids against Aedes aegypti [yellow fever mosquito (Diptera: Culicidae)] using the K & D bioassay system (Klun et al 2005). The saturated fattyacids (C6:0 to C16...

Fattyacid spectra were made on Thiobacillus thiooxidans cultures both in the presence and absence of organic compounds. Small additions of glucose or acetate had no significant effect either on growth or fattyacid content. The addition of biotin had no stimulatory effect but did result in slight quantitative changes in the fattyacid spectrum. The predominant fattyacid was a C19 cyclopropane acid. PMID:4945206

Polyunsaturated fattyacids (PUFAs) are the major components of brain and retina, and are the essential fattyacids with important physiologically active functions. Thus, PUFAs should be provided to children, and are very important in the brain growth and development for fetuses, newborn infants, and children. Omega-3 fattyacids decrease coronary artery disease and improve blood flow. PUFAs have been known to have anti-inflammatory action and improved the chronic inflammation such as auto-immune diseases or degenerative neurologic diseases. PUFAs are used for metabolic syndrome related with obesity or diabetes. However, there are several considerations related with intake of PUFAs. Obsession with the intake of unsaturated fattyacids could bring about the shortage of essential fattyacids that are crucial for our body, weaken the immune system, and increase the risk of heart disease, arrhythmia, and stroke. In this review, we discuss types, physiologic mechanism of action of PUFAs, intake of PUFAs for children, recommended intake of PUFAs, and considerations for the intake of PUFAs. PMID:24224148

Nitro-fattyacids (NO2-FAs) are electrophilic signaling mediators formed in vivo via nitric oxide (NO)- and nitrite (NO2−)-dependent reactions. Nitro-fattyacids modulate signaling cascades via reversible covalent post-translational modification of nucleophilic amino acids in regulatory proteins and enzymes, thus altering downstream signaling events, such as Keap1-Nrf2-antioxidant response element (ARE)-regulated gene expression. In this study, we investigate the molecular mechanisms by which 9- and 10-nitro-octadec-9-enoic acid (OA-NO2) activate the transcription factor Nrf2, focusing on the post-translational modifications of cysteines in the Nrf2 inhibitor Keap1 by nitroalkylation and its downstream responses. Of the two regioisomers, 9-nitro-octadec-9-enoic acid was a more potent ARE inducer than 10-nitro-octadec-9-enoic acid. The most OA-NO2-reactive Cys residues in Keap1 were Cys38, Cys226, Cys257, Cys273, Cys288, and Cys489. Of these, Cys273 and Cys288 accounted for ∼50% of OA-NO2 reactions in a cellular milieu. Notably, Cys151 was among the least OA-NO2-reactive of the Keap1 Cys residues, with mutation of Cys151 having no effect on net OA-NO2 reaction with Keap1 or on ARE activation. Unlike many other Nrf2-activating electrophiles, OA-NO2 enhanced rather than diminished the binding between Keap1 and the Cul3 subunit of the E3 ligase for Nrf2. OA-NO2 can therefore be categorized as a Cys151-independent Nrf2 activator, which in turn can influence the pattern of gene expression and therapeutic actions of nitroalkenes. PMID:21357422

Keloids develop when scar tissue responds to skin trauma with proliferative fibrous growths that extend beyond the boundaries of the original wound and progress for several months or years. Keloids most frequently occur in individuals of indigenous sub-Saharan African origin. The etiology for keloids is still unknown and treatment can be problematic as patients respond differently to various treatment modalities. Keloids have a high rate of recurrence following surgical excision. Some West African patients claim to have had successful outcomes with traditional African remedies-boa constrictor oil (BCO) and shea butter-leading the authors to investigate their effects on cultured fibroblasts. The effects of emulsions of BCO, fish oil, isolated omega-3 fattyacids, and shea butter were tested in comparison to triamcinolone regarding inhibition of cell growth in keloid and control fibroblast cultures. In a series of controlled studies, it was observed that fish oil and BCO were more effective than triamcinolone, and that cis-5, 8, 11, 14, 17-eicosapentaenoic acid was more effective than -linolenic acid. While cell counts in control cultures continuously decreased over a period of 5 days, cell counts in keloid cultures consistently declined between day 1 and day 3, and then increased between day 3 and day 5 for all tested reagents except for fish oil. These results suggest that oils rich in omega-3 fattyacids may be effective in reducing actively proliferating keloid fibroblasts. Additional studies are warranted to investigate whether oils rich in omega-3 fattyacids offer effective and affordable treatment for some keloid patients, especially in the developing world. PMID:24489452

Mitochondrial fattyacid transport is a rate-limiting step in long chain fattyacid (LCFA) oxidation. In rat skeletal muscle, the transport of LCFA at the level of mitochondria is regulated by carnitine palmitoyltransferase I (CPTI) activity and the content of malonyl-CoA (M-CoA); however, this relationship is not consistently observed in humans. Recently, fattyacid translocase (FAT)/CD36 was identified on mitochondria isolated from rat and human skeletal muscle and found to be involved in LCFA oxidation. The present study investigated the effects of exercise (120 min of cycling at ∼60% V̇O2peak) on CPTI palmitoyl-CoA and M-CoA kinetics, and on the presence and functional significance of FAT/CD36 on skeletal muscle mitochondria. Whole body fat oxidation rates progressively increased during exercise (P < 0.05), and concomitantly M-CoA inhibition of CPTI was progressively attenuated. Compared to rest, 120 min of cycling reduced (P < 0.05) the inhibition of 0.7, 2, 5 and 10 μm M-CoA by 16%, 21%, 30% and 34%, respectively. Whole body fat oxidation and palmitate oxidation rates in isolated mitochondria progressively increased (P < 0.05) during exercise, and were positively correlated (r = 0.78). Mitochondrial FAT/CD36 protein increased by 63% (P < 0.05) during exercise and was significantly (P < 0.05) correlated with mitochondrial palmitate oxidation rates at all time points (r= 0.41). However, the strongest (P < 0.05) correlation was observed following 120 min of cycling (r= 0.63). Importantly, the addition of sulfo-N-succimidyloleate, a specific inhibitor of FAT/CD36, reduced mitochondrial palmitate oxidation to ∼20%, indicating FAT/CD36 is functionally significant with respect to LCFA oxidation. We hypothesize that exercise-induced increases in fattyacid oxidation occur as a result of an increased ability to transport LCFA into mitochondria. We further suggest that decreased CPTI M-CoA sensitivity and increased mitochondrial FAT/CD36 protein are both

Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fattyacid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 3 (ω3) fattyacids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 6 (ω6) fattyacids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fattyacids on tumorigenesis, we performed experiments to examine the effects of the ω3 fattyacids EPA and DHA and of the ω6 fattyacid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of ω3 fattyacids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of ω6 to ω3 fattyacids may be a significant factor in mediating tumor development. PMID:11416221

Evidence continues to emerge detailing the myriad of ways the gut microbiota influences host energy homeostasis. Among the potential mechanisms, short chain fattyacids (SCFAs), the byproducts of microbial fermentation of dietary fibers, exhibit correlative beneficial metabolic effects in humans and rodents, including improvements in glucose homeostasis. The underlying mechanisms, however, remain elusive. We here report that one of the main bacterially produced SCFAs, propionate, activates ileal mucosal free fattyacid receptor 2 to trigger a negative feedback pathway to lower hepatic glucose production in healthy rats in vivo We further demonstrate that an ileal glucagon-like peptide-1 receptor-dependent neuronal network is necessary for ileal propionate and long chain fattyacid sensing to regulate glucose homeostasis. These findings highlight the potential to manipulate fattyacid sensing machinery in the ileum to regulate glucose homeostasis. PMID:26896795

In Escherichia coli, FadR and FabR are transcriptional regulators that control the expression of fattyacid degradation and unsaturated fattyacid synthesis genes, depending on the availability of fattyacids. In this report, we focus on the dual transcriptional regulator FadR. In the absence of fattyacids, FadR represses the transcription of fad genes required for fattyacid degradation. However, FadR is also an activator, stimulating transcription of the products of the fabA and fabB genes responsible for unsaturated fattyacid synthesis. In this study, we show that FadR directly activates another fattyacid synthesis promoter, PfabH, which transcribes the fabHDG operon, indicating that FadR is a global regulator of both fattyacid degradation and fattyacid synthesis. We also demonstrate that ppGpp and its cofactor DksA, known primarily for their role in regulation of the synthesis of the translational machinery, directly inhibit transcription from the fabH promoter. ppGpp also inhibits the fadR promoter, thereby reducing transcription activation of fabH by FadR indirectly. Our study shows that both ppGpp and FadR have direct roles in the control of fattyacid promoters, linking expression in response to both translation activity and fattyacid availability. PMID:23772072

Lipoprotein lipase (LPL) was obtained from rat postheparin plasma by chromatographies on heparin-Sepharose and hydroxyapatite. The enzyme was associated with fattyacid ethyl ester synthase (FAEE synthase) as judged by their co-elution profiles and identical profiles of inhibition by diisopropyl fluorophosphate. Only one polypeptide of molecular weight 57,000 in purified LPL fraction was labeled by affinity labeling with [3H]-diisopropyl fluorophosphate. The FAEE synthase activity of LPL was not affected by addition of apolipoprotein C-II. Digestion of the enzyme with trypsin resulted in almost complete loss of the triolein-hydrolyzing activity without change in FAEE synthase activity. The tributyrin-hydrolyzing activity of LPL was also not affected by addition of apolipoprotein C-II or trypsin digestion. On addition at progressively higher concentrations, bovine serum albumin increased FAEE synthesis to a maximum at 2 mg/ml and at higher concentrations inhibited its activity. On incubation of purified LPL with chylomicrons in an ethanol/water mixture, FAEE was formed in the presence of a high concentration of bovine serum albumin. The specific activity of FAEE synthesis from chylomicrons was about 65 times that from oleic acid. Triolein/gum arabic emulsion was used for identification of reaction products. We propose the following mechanism of FAEE formation from chylomicrons by LPL. The enzyme attacks chylomicrons forming an acyl-enzyme intermediate, and during the deacylation process, ethanol binds to fattyacids as an acceptor. These results suggest that LPL contributes to nonoxidative ethanol metabolism (FAEE formation) through degradation of triglyceride-rich lipoproteins such as chylomicrons. PMID:8119932

The mechanism by which diet regulates liver lipogenesis is unclear. Here the authors report how dietary alterations effect the activities of key enzymes of fattyacid (FA) synthesis. Male Sprague-Dawley rats, 400-500 g, were fasted for 48h and then refed a fat-free, high carbohydrate (HC) diet (75% cal. from sucrose) for 0,3,9,24 and 48h, or refed a HC diet for 48h, then fed a high-fat (HF) diet (44% cal. from corn oil) for 3,9,24 and 48h. The FA synthesis rate and the activities of acetyl CoA carboxylase (AC), fattyacid synthase (FAS), ATP citrate lyase (CL), and glucose 6-phosphate dehydrogenase (G6PDH) were determined in the livers. FA synthesis was assayed with /sup 3/H/sub 2/O, enzyme activities were measured spectrophotometrically except for AC which was assayed with /sup 14/C-bicarbonate. There was no change in the activity of AC during fasting or on the HC diet. Fasting decreased the rate of FA synthesis by 25% and the activities of FAS and CL by 50%; refeeding the HC diet induced parallel changes in FA synthesis and the activities of FAS, CL, and G6PDH. After 9h on the HF diet, FA synthesis had decreased sharply, AC activity increased significantly while no changes were detected in the other activities. Subsequently FA synthesis did not change while the activities of the enzymes decreased slowly. These enzymes did not appear to regulate FA synthesis during inhibition of lipogenesis, but FAS, CL or G6PDH may be rate limiting in the induction phase. Other key factors may regulate FA synthesis during dietary alterations.

The traveler participated in the Second International Workshop on Radioiodinated Free FattyAcids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fattyacids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.

Furan fattyacids (F-acids) gain special attentions since they are known to play important roles in biological systems including humans. Specifically F-acids are known to have strong antioxidant activity like radical scavenging activity. Although widely distributed in most biological systems, F-ac...

In this study, we investigated the correlation between the serum fattyacid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fattyacids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fattyacid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fattyacid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fattyacids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fattyacid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. PMID:27179602

Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fattyacids, such as docosahexaenoic acid (DHA, 22:6{omega}-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fattyacid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-{kappa}B (NF-{kappa}B). A{sub 4}/J{sub 4}-neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH{sub 4}), which concurrently abrogated A{sub 4}/J{sub 4}-NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A{sub 4}/J{sub 4} NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5{omega}-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A{sub 4}/J{sub 4}-NPs as mediators of omega-3 fattyacid-mediated protection against the

Coplanar polychlorinated biphenyls (PCBs) may facilitate development of atherosclerosis by stimulating pro-inflammatory pathways in the vascular endothelium. Nutrition, including fish oil-derived long-chain omega-3 fattyacids, such as docosahexaenoic acid (DHA, 22:6ω-3), can reduce inflammation and thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone metabolites produced by oxidation of DHA can protect against PCB-induced endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of the fattyacid with the free radical generator 2,2-azo-bis(2-amidinopropane) dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of superoxide induced by PCB77, and subsequent activation of nuclear factor-κB (NF-κB). A4/J4-neuroprostanes (NPs) were identified and quantitated using HPLC ESI tandem mass spectrometry. Levels of these NPs were markedly increased after DHA oxidation with AAPH.. The protective actions of oxDHA were reversed by treatment with sodium borohydride (NaBH4), which concurrently abrogated A4/J4-NP formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1)by PCB77 was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective effects were proportional to the abundance of A4/J4NPs in the oxidized DHA sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5ω-3) also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2)and downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed protection against PCB77 toxicity. Our data implicate A4/J4-NPs as mediators of omega-3 fattyacid-mediated protection against the endothelial toxicity of coplanar PCBs. PMID:21130106

When inhaled, ozone reacts at the airway luminal surface with unsaturated fattyacids contained in the extracellular fluid and plasma membrane to form an aldehyde and hydroxyhydroperoxide. The resulting hydroxyhydroperoxide degrades in aqueous systems to yield a second aldehyde and hydrogen peroxide (H2O2). Previously, we demonstrated that ozone can augment eicosanoid metabolism in bovine airway epithelial cells. To examine structure-activity relationships of ozone-fattyacid degradation products on eicosanoid metabolism in human airway epithelial cells, 3-, 6-, and 9-carbon saturated aldehydes and hydroxyhydroperoxides were synthesized and purified. Eicosanoid metabolism was evaluated by determination of total 3H-activity release from confluent cells previously incubated with [3H]arachidonic acid and by identification of specific metabolites with high performance liquid chromatography and radioimmunoassay. The major metabolites detected were prostaglandin E2, prostaglandin F2 alpha, and 15-hydroxyeicosatetraenoic acid. The 9-carbon aldehyde, nonanal, in contrast to 3- or 6-carbon aldehydes, stimulated release at concentrations > or = 100 microM, suggesting that the stimulatory effect increases with increasing chain length. When tested under identical conditions, the 3-, 6-, and 9-carbon hydroxyhydroperoxides were more potent than the corresponding aldehydes. Again, a greater effect was noted when the chain length was increased. One possible explanation for the increased potency of the hydroxyhydroperoxides over the aldehydes could be due to degradation of the hydroxyhydroperoxide into H2O2 and aldehyde. We consider this an unlikely explanation because responses varied with chain length (although each hydroxyhydroperoxide would produce an equivalent amount of H2O2) and because exposure to H2O2 alone or H2O2 plus hexanal produced a response dissimilar to 1-hydroxy-1-hexanehydroperoxide.

Culex mosquitoes have emerged as important model organisms for mosquito biology, and are disease vectors for multiple mosquito-borne pathogens, including West Nile virus. We characterized epoxide hydrolase activities in the mosquito Culex quinquefasciatus, which suggested multiple forms of epoxide hydrolases were present. We found EH activities on epoxy eicosatrienoic acids (EETs). EETs and other eicosanoids are well-established lipid signaling molecules in vertebrates. We showed EETs can be synthesized in vitro from arachidonic acids by mosquito lysate, and EETs were also detected in vivo both in larvae and adult mosquitoes by LC-MS/MS. The EH activities on EETs can be induced by blood feeding, and the highest activity was observed in the midgut of female mosquitoes. The enzyme activities on EETs can be inhibited by urea-based inhibitors designed for mammalian soluble epoxide hydrolases (sEH). The sEH inhibitors have been shown to play diverse biological roles in mammalian systems, and they can be useful tools to study the function of EETs in mosquitoes. Besides juvenile hormone metabolism and detoxification, insect epoxide hydrolases may also play a role in regulating lipid signaling molecules, such as EETs and other epoxy fattyacids, synthesized in vivo or obtained from blood feeding by female mosquitoes. PMID:25686802

The yeast Saccharomyces cerevisiae is a facultative anaerobic organism. Under anaerobiosis, sustained growth relies on the presence of exogenously supplied unsaturated fattyacids and ergosterol that yeast is unable to synthesize in the absence of oxygen or upon haem depletion. In the absence of exogenous supplementation with unsaturated fattyacid, a net accumulation of SFA (saturated fattyacid) is observed that induces significant modification of phospholipid profile [Ferreira, Régnacq, Alimardani, Moreau-Vauzelle and Bergès (2004) Biochem. J. 378, 899-908]. In the present paper, we focus on the role of SFH2/CSR1, a hypoxic gene related to SEC14 and its involvement in lipid metabolism upon haem depletion in the absence of oleic acid supplementation. We observed that inactivation of SFH2 results in enhanced accumulation of SFA and phospholipid metabolism alterations. It results in premature growth arrest and leads to an exacerbated sensitivity to exogenous SFA. This phenotype is suppressed in the presence of exogenous oleic acid, or by a controlled expression of FAS1, one of the two genes encoding FAS. We present several lines of evidence to suggest that Sfh2p and oleic acid regulate SFA synthase in yeast at different levels: whereas oleic acid acts on FAS2 at the transcriptional level, we show that Sfh2p inhibits fattyacid synthase activity in response to haem depletion. PMID:17803462

A series of fattyacid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ(9)-trans-HA showed similar activity. Activity due to the different chain length of the saturated fattyacid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists. PMID:25832022

In characterizing the enzymes involved in the formation of very long-chain fattyacids (VLCFAs) in the Brassicaceae, we have generated a series of mutants of Arabidopsis thaliana that have reduced VLCFA content. Here we report the characterization of a seed lipid mutant, AS11, which, in comparison to wild type (WT), has reduced levels of 20:1 and 18:1 and accumulates 18:3 as the major fattyacid in triacylglycerols. Proportions of 18:2 remain similar to WT. Genetic analyses indicate that the fattyacid phenotype is caused by a semidominant mutation in a single nuclear gene, designated TAG1, located on chromosome 2. Biochemical analyses have shown that the AS11 phenotype is not due to a deficiency in the capacity to elongate 18:1 or to an increase in the relative delta 15 or delta 12 desaturase activities. Indeed, the ratio of desaturase/elongase activities measured in vitro is virtually identical in developing WT and AS11 seed homogenates. Rather, the fattyacid phenotype of AS11 is the result of reduced diacylglycerol acyltransferase activity throughout development, such that triacylglycerol biosynthesis is reduced. This leads to a reduction in 20:1 biosynthesis during seed development, leaving more 18:1 available for desaturation. Thus, we have demonstrated that changes to triacylglycerol biosynthesis can result in dramatic changes in fattyacid composition and, in particular, in the accumulation of VLCFAs in seed storage lipids. PMID:7784510

Lipid droplets (LDs) are intracellular organelles that provide fattyacids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

Background: Diabetes is a major cause of death. Oxidative stress mainly caused by hyperglycemia is the primary reason of related complications. Omega-3 fattyacids are prescribed in diabetes but the effect on antioxidant defense is controversial. This study investigated effects of omega-3 supplementation on antioxidant enzymes activity in type 2 diabetic patients. Methods: A randomized, placebo controlled, double blind clinical trial was performed on 90 type2 diabetic patients. The treatment group took, daily, three capsules of omega-3 for two mo, which totally provided 2714mg omega-3 (EPA=1548 mg, DHA=828 mg and 338 mg of other omega=3 fattyacids). Placebo contained 2100 mg sunflower oil (12% SFA, 65% linoleic acid, 23% MUFA), which is the main oil used in the study population. Food intakes, anthropometric and demographic characteristics, and therapeutic regimen data were recorded before and after the intervention. Fasting blood samples were taken before and after the intervention to measure super oxide dismutase, glutathione peroxidase, glutathione reductase, catalase and total antioxidant capacity in erythrocytes. Results: A total of 81 subjects completed the study. Two study groups were similar as regards duration of diabetes, age and the enzymes at baseline. Energy and macro- and micronutrients intakes, weight and hypoglycemic agent consumption were similar in the two groups at baseline and did not change. Supplementation had no effect on antioxidant enzyme status. Glycated hemoglobin showed a significant reduction by supplementation. Conclusion: Daily supplementation of 2714 mg mega-3 for two mo results in a significant reduction in HbA1c level in type2 diabetic patients with no effects on antioxidant enzymes activity. PMID:27141496

In vivo models show that n-3 polyunsaturated fattyacids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc ε receptor I (FcεRI)-mediated signal transduction and mast cell activation. Bone marrow-derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fattyacid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n-3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less β-hexosaminidase (β-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (β-hex release) following FcεRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and FcεRI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell FcεRI was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced FcεRI localization to lipid rafts, and stimulation with antigen resulted in aberrant FcεRI shuttling to the rafts. Our results show that n-3 PUFA suppress FcεRI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FcεRI to lipid rafts. PMID:26363927

The hemolytic activity and solubilizing capacity of two families of non-reducing trisaccharide fattyacid monoesters have been studied to assess their usefulness as surfactants for pharmaceutical applications. The carbohydrate-based surfactants investigated included homologous series of raffinose and melezitose monoesters bearing C10 to C18 acyl chains prepared by lipase-catalyzed synthesis in organic media. The hemolytic activity was determined in vitro using a static method based on the addition of the surfactants to an erythrocyte suspension and subsequent spectrophotometric determination of the released hemoglobin. The effect of the carbohydrate head group, the acyl chain length and the regioisomeric purity was investigated. In all cases, the carbohydrate monoester surfactants decreased their hemolytic activity (with respect to their critical micelle concentration) when increasing the length of the acyl chain. A very similar behaviour was observed either the carbohydrate head-group (raffinose and melezitose) or regardless of the regioisomeric purity. Interestingly, decanoyl (C10) and lauroyl (C12) monoesters were just marginally hemolytic at their critical micelle concentrations while the longer palmitoyl (C16) and (C18) stearoyl monoesters become hemolytic at concentrations much higher than their respective cmc. The palmitoyl and stearoyl monoesters also displayed higher solubilization capacity than the shorter acyl chain monoesters in a solubilization assay of a hydrophobic dye as a model drug mimic. These results suggest that raffinose and melezitose monoesters with long-chain fattyacids (C16 to C18) are promising surfactants for pharmaceutical applications and could be an alternative to the use of current commercial nonionic polyoxyethylene-based surfactants in parenteral formulations. PMID:25753196

Nickel exposure is associated with changes in cellular energy metabolism which may contribute to its carcinogenic properties. Here, we demonstrate that nickel strongly represses mitochondrial fattyacid oxidation—the pathway by which fattyacids are catabolized for energy—in both primary human lung fibroblasts and mouse embryonic fibroblasts. At the concentrations used, nickel suppresses fattyacid oxidation without globally suppressing mitochondrial function as evidenced by increased glucose oxidation to CO2. Pre-treatment with L-carnitine, previously shown to prevent nickel-induced mitochondrial dysfunction in neuroblastoma cells, did not prevent the inhibition of fattyacid oxidation. The effect of nickel on fattyacid oxidation occurred only with prolonged exposure (>5 hr), suggesting that direct inhibition of the active sites of metabolic enzymes is not the mechanism of action. Nickel is a known hypoxia-mimetic that activates hypoxia inducible factor-1α (HIF1α). Nickel-induced inhibition of fattyacid oxidation was blunted in HIF1α knockout fibroblasts, implicating HIF1α as one contributor to the mechanism. Additionally, nickel down-regulated the protein levels of the key fattyacid oxidation enzyme very long-chain acyl-CoA dehydrogenase (VLCAD) in a dose-dependent fashion. In conclusion, inhibition of fattyacid oxidation by nickel, concurrent with increased glucose metabolism, represents a form of metabolic reprogramming that may contribute to nickel-induced carcinogenesis. PMID:26051273

Short-chain fattyacids (SCFAs), the preferred carbon sources for biological nutrient removal, are the important intermediate products in sludge anaerobic fermentation. Sodium dodecylbenzene sulfonate (SDBS) is a widespread used surfactant, which can be easily found in waste-activated sludge (WAS). In this investigation, the effect of SDBS on SCFAs production from WAS was investigated, and the potential of using fermentative SCFAs to promote enhanced biological phosphorus removal (EBPR) was tested. Results showed that the total SCFAs production increased significantly in the presence of SDBS at room temperature. At fermentation time of 6 days, the maximum SCFAs was 2599.1mg chemical oxygen demand (COD)/L in the presence of SDBS 0.02g/g, whereas it was only 339.1mg (COD)/L in the absence of SDBS. The SCFAs produced in the case of SDBS 0.02g/g and fermentation time 6 days consisted of acetic acid (27.1%), propionic acid (22.8%), iso-valeric acid (20.1%), iso-butyric acid (11.9%), n-butyric acid (10.4%) and n-valeric acid (7.7%). It was found that during sludge anaerobic fermentation, the solubilization of sludge particulate organic-carbon and hydrolysis of solubilized substrate as well as acidification of hydrolyzed products were all increased in the presence of SDBS, while the methane formation was decreased, the SCFAs production was therefore remarkably improved. Further investigation showed that the production of SCFAs enhanced by SDBS was caused mainly by biological effects, rather than by chemical effects and SDBS decomposition. With the fermentative SCFAs as the main carbon source, the EBPR maintained high phosphorus removal efficiency ( approximately 97%). PMID:17499838

Degradation of unusual fattyacids through β-oxidation within transgenic plants has long been hypothesized as a major factor limiting the production of industrially useful unusual fattyacids in seed oils. Arabidopsis seeds expressing the castor fattyacid hydroxylase accumulate hydroxylated fattyacids up to 17% of total fattyacids in seed triacylglycerols; however, total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acetate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fattyacid synthesis within the transgenic seeds was approximately half that of control seeds. RNAseq analysis indicated no changes in expression of fattyacid synthesis genes in hydroxylase-expressing plants. However, differential [14C]acetate and [14C]malonate metabolic labeling of hydroxylase-expressing seeds indicated the in vivo acetyl–CoA carboxylase activity was reduced to approximately half that of control seeds. Therefore, the reduction of oil content in the transgenic seeds is consistent with reduced de novo fattyacid synthesis in the plastid rather than fattyacid degradation. Intriguingly, the coexpression of triacylglycerol synthesis isozymes from castor along with the fattyacid hydroxylase alleviated the reduced acetyl–CoA carboxylase activity, restored the rate of fattyacid synthesis, and the accumulation of seed oil was substantially recovered. Together these results suggest a previously unidentified mechanism that detects inefficient utilization of unusual fattyacids within the endoplasmic reticulum and activates an endogenous pathway for posttranslational reduction of fattyacid synthesis within the plastid. PMID:24398521

Anaerobic co-fermentation of waste activated sludge (WAS) and henna plant biomass (HPB) for the enhanced production of volatile fattyacids (VFAs) was investigated. The results indicated that VFAs was the main constituents of the released organics; the accumulation of VFAs was much higher than that of soluble carbohydrates and proteins. HPB was an advantageous substrate compared to WAS for VFAs production; and the maximum VFAs concentration in an HPB mono-fermentation system was about 2.6-fold that in a WAS mono-fermentation system. In co-fermentation systems, VFAs accumulation was positively related to the proportion of HPB in the mixed substrate, and the accumulated VFAs concentrations doubled when HPB was increased from 25% to 75%. HPB not only adjust the C/N ratio; the associated and/or released lawsone might also have a positive electron-shuttling effect on VFAs production. PMID:27003793

Waste activated sludge (WAS) fermentation integrated with denitritation (the reduction of nitrite to dinitrogen gas) at different pHs was investigated in batch-mode reactors over a 24-day period. The results showed that in comparison with controlled pHs, the volatile fattyacid (VFA) bioproduction for in situ denitritation was significantly improved at uncontrolled pH. VFA fermented from WAS was quickly consumed by denitritation at uncontrolled pH, which accelerated sludge degradation. On the other hand, sludge digestion was benefited from the alkalinity produced from denitritation, while methanogenesis was prohibited by alkalinity and nitrite. The integrated sludge fermentation and denitritation can be cost-effectively applied to wastewater treatment plants, so that organic substrates (e.g., VFAs) are produced for denitritation via simultaneous sludge fermentation, which enables WAS reutilization and enhances nitrogen removal efficiency without the need of external carbon sources. PMID:26475401

The short chain fattyacid receptor FFA2 is able to stimulate signaling via both Gi- and Gq/G11-promoted pathways. These pathways are believed to control distinct physiological end points but FFA2 receptor ligands appropriate to test this hypothesis have been lacking. Herein, we characterize AZ1729, a novel FFA2 regulator that acts as a direct allosteric agonist and as a positive allosteric modulator, increasing the activity of the endogenously produced short chain fattyacid propionate in Gi-mediated pathways, but not at those transduced by Gq/G11. Using AZ1729 in combination with direct inhibitors of Gi and Gq/G11 family G proteins demonstrated that although both arms contribute to propionate-mediated regulation of phospho-ERK1/2 MAP kinase signaling in FFA2-expressing 293 cells, the Gq/G11-mediated pathway is predominant. We extend these studies by employing AZ1729 to dissect physiological FFA2 signaling pathways. The capacity of AZ1729 to act at FFA2 receptors to inhibit β-adrenoreceptor agonist-promoted lipolysis in primary mouse adipocytes and to promote chemotaxis of isolated human neutrophils confirmed these as FFA2 processes mediated by Gi signaling, whereas, in concert with blockade by the Gq/G11 inhibitor FR900359, the inability of AZ1729 to mimic or regulate propionate-mediated release of GLP-1 from mouse colonic preparations defined this physiological response as an end point transduced via activation of Gq/G11. PMID:27385588

The short chain fattyacid receptor FFA2 is able to stimulate signaling via both Gi- and Gq/G11-promoted pathways. These pathways are believed to control distinct physiological end points but FFA2 receptor ligands appropriate to test this hypothesis have been lacking. Herein, we characterize AZ1729, a novel FFA2 regulator that acts as a direct allosteric agonist and as a positive allosteric modulator, increasing the activity of the endogenously produced short chain fattyacid propionate in Gi-mediated pathways, but not at those transduced by Gq/G11 Using AZ1729 in combination with direct inhibitors of Gi and Gq/G11 family G proteins demonstrated that although both arms contribute to propionate-mediated regulation of phospho-ERK1/2 MAP kinase signaling in FFA2-expressing 293 cells, the Gq/G11-mediated pathway is predominant. We extend these studies by employing AZ1729 to dissect physiological FFA2 signaling pathways. The capacity of AZ1729 to act at FFA2 receptors to inhibit β-adrenoreceptor agonist-promoted lipolysis in primary mouse adipocytes and to promote chemotaxis of isolated human neutrophils confirmed these as FFA2 processes mediated by Gi signaling, whereas, in concert with blockade by the Gq/G11 inhibitor FR900359, the inability of AZ1729 to mimic or regulate propionate-mediated release of GLP-1 from mouse colonic preparations defined this physiological response as an end point transduced via activation of Gq/G11. PMID:27385588

N-Acylethanolamines (NAEs) are involved in numerous biological activities in plant and animal systems. The metabolism of these lipids by fattyacid amide hydrolase (FAAH) is a key regulatory point in NAE signaling activity. Several active site-directed inhibitors of FAAH have been identified, but few compounds have been described that enhance FAAH activity. Here we synthesized two sets of phenoxyacyl-ethanolamides from natural products, 3-n-pentadecylphenolethanolamide and cardanolethanolamide, with structural similarity to NAEs and characterized their effects on the hydrolytic activity of FAAH. Both compounds increased the apparent Vmax of recombinant FAAH proteins from both plant (Arabidopsis) and mammalian (Rattus) sources. These NAE-like compounds appeared to act by reducing the negative feedback regulation of FAAH activity by free ethanolamine. Both compounds added to seedlings relieved, in part, the negative growth effects of exogenous NAE12:0. Cardanolethanolamide reduced neuronal viability and exacerbated oxidative stress-mediated cell death in primary cultured neurons at nanomolar concentrations. This was reversed by FAAH inhibitors or exogenous NAE substrate. Collectively, our data suggest that these phenoxyacyl-ethanolamides act to enhance the activity of FAAH and may stimulate the turnover of NAEs in vivo. Hence, these compounds might be useful pharmacological tools for manipulating FAAH-mediated regulation of NAE signaling in plants or animals. PMID:24558037

N-Acylethanolamines (NAEs) are involved in numerous biological activities in plant and animal systems. The metabolism of these lipids by fattyacid amide hydrolase (FAAH) is a key regulatory point in NAE signaling activity. Several active site-directed inhibitors of FAAH have been identified, but few compounds have been described that enhance FAAH activity. Here we synthesized two sets of phenoxyacyl-ethanolamides from natural products, 3-n-pentadecylphenolethanolamide and cardanolethanolamide, with structural similarity to NAEs and characterized their effects on the hydrolytic activity of FAAH. Both compounds increased the apparent Vmax of recombinant FAAH proteins from both plant (Arabidopsis) and mammalian (Rattus) sources. These NAE-like compounds appeared to act by reducing the negative feedback regulation of FAAH activity by free ethanolamine. Both compounds added to seedlings relieved, in part, the negative growth effects of exogenous NAE12:0. Cardanolethanolamide reduced neuronal viability and exacerbated oxidative stress-mediated cell death in primary cultured neurons at nanomolar concentrations. This was reversed by FAAH inhibitors or exogenous NAE substrate. Collectively, our data suggest that these phenoxyacyl-ethanolamides act to enhance the activity of FAAH and may stimulate the turnover of NAEs in vivo. Hence, these compounds might be useful pharmacological tools for manipulating FAAH-mediated regulation of NAE signaling in plants or animals. PMID:24558037

This study was conceived to evaluate the essential fattyacids, secondary metabolites, antiradical and antimicrobial activities of unexploited Tunisian Ziziphus lotus L. The obtained results indicated that the major components of fattyacids were oleic acid (88.12%) and elaidic acid (7.88%). Leaves contained higher amount of total phenols, flavonoids and tannins than fruits, although both methanolic extracts had significant antioxidant activities. Significant correlations were observed between the total phenol or flavonoid contents in methanolic extracts and antioxidant activity estimated by using both 2,2'-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic radical-scavenging methods. In addition, both methanolic extracts exhibited strong antibacterial and antifungal activities. The inhibition zone diameters and the minimal inhibition concentration values were in the range of 10-17 mm and 3.1-50 mg/mL, respectively. PMID:24805194

In both animal and plant acyl elongation systems, it has been proposed that fattyacids are first activated to acyl-coenzyme A (CoA) before their elongation, and that the ATP dependence of fattyacid elongation is evidence of acyl-CoA synthetase involvement. However, because CoA is not supplied in standard fattyacid elongation assays, it is not clear if CoA-dependent acyl-CoA synthetase activity can provide levels of acyl-CoAs necessary to support typical rates of fattyacid elongation. Therefore, we examined the role of acyl-CoA synthetase in providing the primer for acyl elongation in leek (Allium porrum L.) epidermal microsomes and Brassica napus L. cv Reston oil bodies. As presented here, fattyacid elongation was independent of CoA and proceeded at maximum rates with CoA-free preparations of malonyl-CoA. We also showed that stearic acid ([1-14C]18:0)-CoA was synthesized from [1-14C]18:0 in the presence of CoA-free malonyl-CoA or acetyl-CoA, and that [1-14C]18:0-CoA synthesis under these conditions was ATP dependent. Furthermore, the appearance of [1-14C]18:0 in the acyl-CoA fraction was simultaneous with its appearance in phosphatidylcholine. These data, together with the s of a previous study (A. Hlousek-Radojcic, H. Imai, J.G. Jaworski [1995] Plant J 8: 803–809) showing that exogenous [14C]acyl-CoAs are diluted by a relatively large endogenous pool before they are elongated, strongly indicated that acyl-CoA synthetase did not play a direct role in fattyacid elongation, and that phosphatidylcholine or another glycerolipid was a more likely source of elongation primers than acyl-CoAs.

New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fattyacids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32-1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15-30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

New compounds are needed to treat acne and superficial infections caused by Propionibacterium acnes and Staphylococcus aureus due to the reduced effectiveness of agents used at present. Long-chain polyunsaturated fattyacids (LC-PUFAs) are attracting attention as potential new topical treatments for Gram-positive infections due to their antimicrobial potency and anti-inflammatory properties. This present study aimed to investigate the antimicrobial effects of six LC-PUFAs against P. acnes and S. aureus to evaluate their potential to treat infections caused by these pathogens. Minimum inhibitory concentrations were determined against P. acnes and S. aureus, and the LC-PUFAs were found to inhibit bacterial growth at 32–1024 mg/L. Generally, P. acnes was more susceptible to the growth inhibitory actions of LC-PUFAs, but these compounds were bactericidal only for S. aureus. This is the first report of antibacterial activity attributed to 15-hydroxyeicosapentaenoic acid (15-OHEPA) and 15-hydroxyeicosatrienoic acid (HETrE), while the anti-P. acnes effects of the six LC-PUFAs used herein are novel observations. During exposure to the LC-PUFAs, S. aureus cells were killed within 15–30 min. Checkerboard assays demonstrated that the LC-PUFAs did not antagonise the antimicrobial potency of clinical agents used presently against P. acnes and S. aureus. However, importantly, synergistic interactions against S. aureus were detected for combinations of benzoyl peroxide with 15-OHEPA, dihomo-γ-linolenic acid (DGLA) and HETrE; and neomycin with 15-OHEPA, DGLA, eicosapentaenoic acid, γ-linolenic acid and HETrE. In conclusion, LC-PUFAs warrant further evaluation as possible new agents to treat skin infections caused by P. acnes and S. aureus, especially in synergistic combinations with antimicrobial agents already used clinically. PMID:24232668

A number of reports indicate that a long-chain free fattyacid export system may be operating in mitochondria. In this study, we sought evidence of its existence in rat heart mitochondria. To determine its potential role, we also sought evidence of its activation or inhibition in streptozotocin (STZ)-induced diabetic rat heart mitochondria. If confirmed, it could be a novel mechanism for regulation of long-chain fattyacid oxidation (FAO) in mitochondria. To obtain evidence of its existence, we tested whether heart mitochondria presented with palmitoyl-carnitine can generate and export palmitate. We found that intact mitochondria indeed generate and export palmitate. We have also found that the rates of these processes are markedly higher in STZ-diabetic rat heart mitochondria, in which palmitoyl-carnitine oxidation is also increased. Since mitochondrial thioesterase-1 (MTE-1) hydrolyzes acyl-CoA to CoA-SH + free fattyacid, and uncoupling protein-3 (UCP-3), reconstituted in liposomes, transports free fattyacids, we examined whether these proteins are also increased in STZ-diabetic rat heart mitochondria. We found that both of these proteins are indeed increased. Gene expression profile analysis revealed striking expression of mitochondrial long-chain fattyacid transport and oxidation genes, accompanying overexpression of MTE-1 and UCP-3 in STZ-diabetic rat hearts. Our findings provide the first direct evidence for the existence of a long-chain free fattyacid generation and export system in mitochondria and its activation in STZ-diabetic rat hearts in which FAO is enhanced. We suggest that its activation may facilitate, and inhibition may limit, enhancement of FAO. PMID:16855217

Described are hosts for overproducing a fattyacid product such as a fattyacid. The hosts include an exogenous nucleic acid encoding a thioesterase and, optionally, an exogenous nucleic acid encoding an acetyl-CoA carboxylase, wherein an acyl-CoA synthetase in the hosts are functionally delected. The hosts prefereably include the nucleic acid encoding the thioesterase at an intermediate copy number. The hosts are preferably recominantly stable and growth-competent at 37.degree. C. Methods of producing a fattyacid product comprising culturing such hosts at 37.degree. C. are also described.

Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fattyacid β-oxidation was used as a tool to study fattyacid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0.06 mg g−1 dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward β-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fattyacids into triacylglycerides by recycling the fattyacids via β-oxidation and that a considerable flow toward β-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids. PMID:10594123

Nitrated fattyacids (NFAs), endogenous products of nonenzymatic reactions of NO-derived reactive nitrogen species with unsaturated fattyacids, exhibit substantial anti-inflammatory activities. They are both reversible electrophiles and peroxisome proliferator-activated receptor γ (PPARγ) agonists, but the physiological implications of their electrophilic activity are poorly understood. We tested their effects on inflammatory and emphysema-related biomarkers in alveolar macrophages (AMs) of smoke-exposed mice. NFA (10-nitro-oleic acid or 12-nitrolinoleic acid) treatment downregulated expression and activity of the inflammatory transcription factor NF-κB while upregulating those of PPARγ. It also downregulated production of inflammatory cytokines and chemokines and of the protease cathepsin S (Cat S), a key mediator of emphysematous septal destruction. Cat S downregulation was accompanied by decreased AM elastolytic activity, a major mechanism of septal destruction. NFAs downregulated both Cat S expression and activity in AMs of wild-type mice, but only inhibited its activity in AMs of PPARγ knockout mice, pointing to a PPARγ-independent mechanism of enzyme inhibition. We hypothesized that this mechanism was electrophilic S-alkylation of target Cat S cysteines, and found that NFAs bind directly to Cat S following treatment of intact AMs and, as suggested by in silico modeling and calculation of relevant parameters, elicit S-alkylation of Cys25 when incubated with purified Cat S. These results demonstrate that NFAs’ electrophilic activity, in addition to their role as PPARγ agonists, underlies their protective effects in chronic obstructive pulmonary disease (COPD) and support their therapeutic potential in this disease. PMID:27119365

Infections with Phytophthora infestans, the causal agent of potato and tomato late blight disease, are difficult to control and can lead to considerable agricultural losses. Thus, the development of new effective agents against the pathogen is of great interest. In previous work, (E)-4-oxohexadec-2-enoic acid (3) was isolated from Hygrophorus eburneus, which exhibited fungicidal activity against Cladosporium cucumerinum. Here, the inhibitory effect of 3 on P. infestans spore germination and mycelium growth in vitro is demonstrated. The in vivo effect on infections of whole potato plants was investigated by spraying plants with the sodium salt of 3, sodium (2E)-4-oxohexadec-2-enoic acid (4), prior to P. infestans inoculation. Additionally, the influence of 3 on mycelium growth of Colletotrichum coccodes, the causal agent of potato black dot disease, was analyzed. In all approaches, a significant inhibition of pathogen development was achieved. Importantly, the unsaturated fattyacid exerted no toxic effect when sprayed on plants, a prerequisite for its commercial use. PMID:19778058

Exercise is considered to be beneficial for free fattyacid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 +/- 10% higher (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 +/- 4.3 versus 9.0 +/- 6.1 micromol (100 ml)(-1) min(-1), P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

Inhibitors of fattyacid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

Adaptation to nutrient scarcity depends on the activation of metabolic programs to efficiently use internal reserves of energy. Activation of these programs in abundant food regimens can extend life span. However, the common molecular and metabolic changes that promote adaptation to nutritional stress and extend life span are mostly unknown. Here we present a response to fasting, enrichment of ω-6 polyunsaturated fattyacids (PUFAs), which promotes starvation resistance and extends Caenorhabditis elegans life span. Upon fasting, C. elegans induces the expression of a lipase, which in turn leads to an enrichment of ω-6 PUFAs. Supplementing C. elegans culture media with these ω-6 PUFAs increases their resistance to starvation and extends their life span in conditions of food abundance. Supplementation of C. elegans or human epithelial cells with these ω-6 PUFAs activates autophagy, a cell recycling mechanism that promotes starvation survival and slows aging. Inactivation of C. elegans autophagy components reverses the increase in life span conferred by supplementing the C. elegans diet with these fasting-enriched ω-6 PUFAs. We propose that the salubrious effects of dietary supplementation with ω-3/6 PUFAs (fish oils) that have emerged from epidemiological studies in humans may be due to a similar activation of autophagic programs. PMID:23392608

The effect of the addition of compatible solutes (ectoine and trehalose) on the denitrification process of saline wastewater was studied. In saline wastewater, it was observed that the initial concentration of nitrates was 500 mg N l⁻¹. A fatty substance isolated from oiled bleaching earth (waste of vegetable oil refining process) was used as a source of carbon.The consortium, which was responsible for the denitrification process originated from the wastewater of the vegetable oil industry. The consortium of microorganisms was identified by the use of restriction fragment length polymorphism of 16S rRNA gene amplicons and sequencing techniques. It was noted that ectoine affects significantly the activity of lipase and nitrate reductase, and resulted in faster denitrification compared to saline wastewater with the addition of trehalose or control saline wastewater (without compatible solutes). It was observed that relative enzyme activities of lipase and nitrate reductase increased by 32 and 35%, respectively, in the presence of 1 mM ectoine. This resulted in an increase in specific nitrate reduction rate in the presence of 1 mM ectoine to 5.7 mg N g⁻¹ VSS h⁻¹, which was higher than in the absence of ectoine (3.2 mg N g⁻¹ VSS h⁻¹). The addition of trehalose did not have an effect on nitrate removals. Moreover, it was found that trehalose was used up completely by bacteria as a source of carbon in the denitrification process. The fattyacids were biodegraded by 74% in the presence of 1 mM ectoine. PMID:22286267

The metabolic function of the liver changes sequentially during early life in mammals to adapt to the marked changes in nutritional environment. Accordingly, hepatic fattyacid β-oxidation is activated after birth to produce energy from breast milk lipids. However, how it is induced during the neonatal period is poorly understood. Here we show DNA demethylation and increased mRNA expression of the fattyacid β-oxidation genes in the postnatal mouse liver. The DNA demethylation does not occur in the fetal mouse liver under the physiologic condition, suggesting that it is specific to the neonatal period. Analysis of mice deficient in the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) and maternal administration of a PPARα ligand during the gestation and lactation periods reveal that the DNA demethylation is PPARα dependent. We also find that DNA methylation of the fattyacid β-oxidation genes are reduced in the adult human liver relative to the fetal liver. This study represents the first demonstration that the ligand-activated PPARα-dependent DNA demethylation regulates the hepatic fattyacid β-oxidation genes during the neonatal period, thereby highlighting the role of a lipid-sensing nuclear receptor in the gene- and life-stage-specific DNA demethylation of a particular metabolic pathway. PMID:25311726

Endothermy, high basal metabolic rates (BMRs), and high locomotor-related metabolism were important steps in the evolution of mammals. It has been proposed that the composition of membrane phospholipid fattyacids plays an important role in energy metabolism and exercise muscle physiology. In particular, the membrane pacemaker theory of metabolism suggests that an increase in cell membrane fattyacid unsaturation would result in an increase in BMR. We aimed to determine whether membrane phospholipid fattyacid composition of heart, liver, and gastrocnemius muscles differed between lines of bank voles selected for high swim-induced aerobic metabolism-which also evolved an increased BMR-and unselected control lines. Proportions of fattyacids significantly differed among the organs: liver was the least unsaturated, whereas the gastrocnemius muscles were most unsaturated. However, fattyacid proportions of the heart and liver did not differ significantly between selected and control lines. In gastrocnemius muscles, significant differences between selection directions were found: compared to control lines, membranes of selected voles were richer in saturated C18:0 and unsaturated C18:2n-6 and C18:3n-3, whereas the pattern was reversed for saturated C16:0 and unsaturated C20:4n-6. Neither unsaturation index nor other combined indexes of fattyacid proportions differed between lines. Thus, our results do not support the membrane pacemaker hypothesis. However, the differences between selected and control lines in gastrocnemius muscles reflect chain lengths rather than number of double bonds and are probably related to differences in locomotor activity per se rather than to differences in the basal or routine metabolic rate. PMID:26658414

In both eukaryotes and prokaryotes, fattyacid synthases are responsible for the biosynthesis of fattyacids in an iterative process, extending the fattyacid by two carbon units every cycle. Thus, odd numbered fattyacids are rarely found in nature. We tested whether representatives of diverse microbial phyla have the ability to incorporate odd-chain fattyacids as substrates for their fattyacid synthases and their downstream enzymes. We fed various odd and short chain fattyacids to the bacterium Escherichia coli, cyanobacterium Synechocystis sp. PCC 6803, green microalga Chlamydomonas reinhardtii and diatom Thalassiosira pseudonana. Major differences were observed, specifically in the ability among species to incorporate and elongate short chain fattyacids. We demonstrate that E. coli, C. reinhardtii, and T. pseudonana can produce longer fattyacid products from short chain precursors (C3 and C5), while Synechocystis sp. PCC 6803 lacks this ability. However, Synechocystis can incorporate and elongate longer chain fattyacids due to acyl-acyl carrier protein synthetase (AasS) activity, and knockout of this protein eliminates the ability to incorporate these fattyacids. In addition, expression of a characterized AasS from Vibrio harveyii confers a similar capability to E. coli. The ability to desaturate exogenously added fattyacids was only observed in Synechocystis and C. reinhardtii. We further probed fattyacid metabolism of these organisms by feeding desaturase inhibitors to test the specificity of long-chain fattyacid desaturases. In particular, supplementation with thia fattyacids can alter fattyacid profiles based on the location of the sulfur in the chain. We show that coupling sensitive gas chromatography mass spectrometry to supplementation of unnatural fattyacids can reveal major differences between fattyacid metabolism in various organisms. Often unnatural fattyacids have antibacterial or even therapeutic properties. Feeding of short

The FATTYACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fattyacids in the seed. The product of the FAE1 gene is presumed to be a condensing enzyme that extends the chain length of fattyacids from C18 to C20 and C22. We report here the cloning of FAE1 by directed transposon tagging with the maize element Activator (Ac). An unstable fae1 mutant was isolated in a line carrying Ac linked to the FAE1 locus on chromosome 4. Cosegregation and reversion analyses established that the new mutant was tagged by Ac. A DNA fragment flanking Ac was cloned by inverse polymerase chain reaction and used to isolate FAE1 genomic clones and a cDNA clone from a library made from immature siliques. The predicted amino acid sequence of the FAE1 protein shares homology with those of other condensing enzymes (chalcone synthase, stilbene synthases, and beta-ketoacyl-acyl carrier protein synthase III), supporting the notion that FAE1 is the structural gene for a synthase or condensing enzyme. FAE1 is expressed in developing seed, but not in leaves, as expected from the effect of the fae1 mutation on the fattyacid compositions of those tissues. PMID:7734965

Composition of fattyacids, tocopherols, tocotrienols, and carotenoids, and their contribution to antioxidant activities were investigated in seeds of three coloured quinoa cultivars (white, red and black). The major components and individual compounds were significantly different, and their concentrations were higher in darker seeds (p < 0.05). The oil yield was 6.58-7.17% which contained predominantly unsaturated fattyacids (89.42%). The ratio of omega-6/omega-3 fattyacid was ca. 6/1. The total tocopherol content ranged from 37.49 to 59.82 μg/g and mainly consisted of γ-tocopherol. Trace amount of α- and β-tocotrienols was also found. Black quinoa had the highest vitamin E followed by red and white quinoas. Carotenoids, mainly trans-lutein (84.7-85.6%) and zeaxanthin were confirmed for the first time in quinoa seeds, and the concentration was also the highest in black seeds. The antioxidant activities of lipophilic extracts were positively correlated with polyunsaturated fattyacids, total carotenoids and total tocopherols. PMID:25529712

In yeast, β-oxidation of fattyacids (FAs) essentially takes place in peroxisomes, and FA activation must precede FA oxidation. In Saccharomyces cerevisiae, a single fatty-acyl–CoA-synthetase, ScFaa2p, mediates peroxisomal FA activation. We have previously shown that this reaction also exists in the oleaginous yeast Yarrowia lipolytica; however, the protein involved in this process remains unknown. Here, we found that proteins, named Aal proteins (Acyl/Aryl-CoA-ligases), resembling the 4-coumarate–CoA-ligase-like enzymes found in plants are involved in peroxisomal FA activation in Y. lipolytica; Y. lipolytica has 10 AAL genes, eight of which are upregulated by oleate. All the Aal proteins contain a PTS1-type peroxisomal targeting sequence (A/SKL), suggesting a peroxisomal localization. The function of the Aal proteins was analyzed using the faa1Δant1Δ mutant strain, which demonstrates neither cytoplasmic FA activation (direct result of FAA1 deletion) nor peroxisomal FA activation (indirect result of ANT1 deletion, a gene coding an ATP transporter). This strain is thus highly sensitive to external FA levels and unable to store external FAs in lipid bodies (LBs). Whereas the overexpression of (cytoplasmic) AAL1ΔPTS1 was able to partially complement the growth defect observed in the faa1Δant1Δ mutant on short-, medium- and long-chain FA media, the presence of Aal2p to Aal10p only allowed growth on the short-chain FA medium. Additionally, partial LB formation was observed in the oleate medium for strains overexpressing Aal1ΔPTS1p, Aal4ΔPTS1p, Aal7ΔPTS1p, and Aal8ΔPTS1p. Finally, an analysis of the FA content of cells grown in the oleate medium suggested that Aal4p and Aal6p present substrate specificity for C16:1 and/or C18:0. PMID:27067366

Polyunsaturated fattyacids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fattyacid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fattyacids in their diet. Many studies on fattyacid desaturases as well as PUFAs have shown that fattyacid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fattyacid metabolism. PMID:26742061

Polyunsaturated fattyacids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fattyacid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fattyacids in their diet. Many studies on fattyacid desaturases as well as PUFAs have shown that fattyacid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fattyacid metabolism. PMID:26742061

Batch test were performed to assess nitrite removal, nitrate formation, CO2 fixation, gaseous nitrogen production and microbial density in activated sludge exposed to volatile fattyacid (VFA) mixtures. Nitrite removal and nitrate formation were both affected by the presence of VFAs, but to different degrees. Nitrate formation rates were reduced to a greater extent (79%) than nitrite removal rates (36%) resulting in an apparent unbalanced nitrite oxidation reaction. Since the total bacterial density and the nitrite oxidizing bacteria (NOB, Nitrospira) concentration remained essentially constant under all test conditions, the reduction in rates was not due to heterotrophic uptake of nitrogen or to a decrease in the NOB population. In contrast to the nitrogen results, VFAs were not found to impact CO2 fixation efficiency. It appeared that nitrite oxidation occurred when VFAs were present since the oxidation of nitrite provides energy for CO2 fixation. However, nitrate produced from the oxidation of nitrite was reduced to gaseous nitrogen products. N2O gas was detected in the presence of VFAs which was a clear indication that VFAs stimulated an alternative pathway, such as aerobic denitrification, during biotransformation of nitrogen in activated sludge. PMID:16436292

The increase of n-6 polyunsaturated fattyacids (PUFA) in animal tissues has been proposed as a mechanism of Pb poisoning through lipid peroxidation or altered eicosanoids metabolism. We have studied fattyacid (FA) composition in liver and brain of mallards (Anas platyrhynchos) feeding for three weeks on diets containing combinations of low or high levels of vitamin E (20 or 200 UI/kg) and Pb (0 or 2 g/kg). Saturated FA, n-6 PUFA and total concentrations of FA were higher in livers of Pb-exposed mallards, but not in their brains. The percentage of n-6 PUFA in liver and brain was slightly higher in Pb-exposed mallards. The increase of n-6 PUFA in liver was associated with increased triglycerides and cholesterol in plasma, thus could be in part attributed to feed refusal and fat mobilization. The hepatic ratios between adrenic acid (22:4 n-6) and arachidonic acid (20:4 n-6) or between adrenic acid and linoleic acid (18:2 n-6) were higher in Pb exposed birds, supporting the existing hypothesis of increased fattyacid elongation by Pb. Among the possible consequences of increased n-6 PUFA concentration in tissues, we found increased lipid peroxidation in liver without important histopathological changes, and decreased plasma alkaline phosphatase activity that may reflect altered bone metabolism in birds.

Recently, the use of waste activated sludge to bioproduce short-chain fattyacids (SCFA) has attracted much attention as the sludge-derived SCFA can be used as a preferred carbon source to drive biological nutrient removal or biopolymer (polyhydroxyalkanoates) synthesis. Although large number of humic acid (HA) has been reported in sludge, the influence of HA on SCFA production has never been documented. This study investigated the effects on sludge-derived SCFA production of two commercially available humic acids (referred to as SHHA and SAHA purchased respectively from Shanghai Reagent Company and Sigma-Aldrich) that differ in chemical structure, hydrophobicity, surfactant properties, and degree of aromaticity. It was found that SHHA remarkably enhanced SCFA production (1.7-3.5 folds), while SAHA had no obvious effect. Mechanisms study revealed that all four steps (solubilization, hydrolysis, acidification, and methanogenesis) involved in sludge fermentation were unaffected by SAHA. However, SHHA remarkably improved the solubilization of sludge protein and carbohydrate and the activity of hydrolysis enzymes (protease and α-glucosidase) owing to its greater hydrophobicity and protection of enzyme activity. SHHA also enhanced the acidification step by accelerating the bioreactions of glyceradehyde-3P → d-glycerate 1,3-diphosphate, and pyruvate → acetyl-CoA due to its abundant quinone groups which served as electron acceptor. Further investigation showed that SHHA negatively influenced the activity of acetoclastic methanogens for its competition for electrons and inhibition on the reaction of acetyl-CoA → 5-methyl-THMPT, which caused less SCFA being consumed. All these observations were in correspondence with SHHA significantly enhancing the production of sludge derived SCFA. PMID:25825920

Fattyacids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fattyacid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fattyacid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fattyacid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fattyacids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fattyacid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fattyacid synthases’ many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fattyacid synthases, providing some clues to important challenges and opportunities in the field. PMID:25360565

Fattyacids are primary metabolites synthesized by complex, elegant, and essential biosynthetic machinery. Fattyacid synthases resemble an iterative assembly line, with an acyl carrier protein conveying the growing fattyacid to necessary enzymatic domains for modification. Each catalytic domain is a unique enzyme spanning a wide range of folds and structures. Although they harbor the same enzymatic activities, two different types of fattyacid synthase architectures are observed in nature. During recent years, strained petroleum supplies have driven interest in engineering organisms to either produce more fattyacids or specific high value products. Such efforts require a fundamental understanding of the enzymatic activities and regulation of fattyacid synthases. Despite more than one hundred years of research, we continue to learn new lessons about fattyacid synthases' many intricate structural and regulatory elements. In this review, we summarize each enzymatic domain and discuss efforts to engineer fattyacid synthases, providing some clues to important challenges and opportunities in the field. PMID:25360565

A new approach to obtain optically active unsaturated or polyunsaturated systems with a single fluorine atom in an allylic or propargylic position is reported. Central to this strategy is the high regio- and stereocontrol observed during the fluorination of propargylic alcohols allowing a short and efficient synthesis of 1. Further, simple functional group transformations gave the enals 2 and 3. These three key intermediates were used for the preparation of optically active monofluorinated analogues of fattyacid metabolites. PMID:11325281

Volatile fattyacids (VFAs) are essential for removing biological nitrogen and phosphorus in wastewater treatment plants. The purpose of this work was to investigate whether and how the addition of NaCl could improve the production of VFAs from waste activated sludge (WAS). Sludge solubilization was efficiently improved by the addition of NaCl. Both protein and carbohydrate in the fermentation liquid increased with the dosage of NaCl, and it provided a larger amount of organic compounds for the production of the VFAs. NaCl had inhibitory effects on the production of methane and a high dosage of NaCl could severely suppress the growth of methanogens, which decreased the consumption of the VFAs. Consequently, the production of VFAs was significantly enhanced by the addition of NaCl. The maximum production of VFAs was achieved with the highest dosage of NaCl (3316 mg (COD)/L at the NaCl dosage 0.5 mol/L; 783 mg (COD)/L without the addition of NaCl). Therefore, this study indicates that using NaCl could be an efficient method for improving the production of VFAs from WAS. PMID:26320405

A systematic study of the structure–activity relationships (SAR) of 2b (OL-135), a potent inhibitor of fattyacid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, Ki = 2.6 nM) with 5hh (aryl = 3-Cl-Ph, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally-restricted C2 side chains were examined and many provided exceptionally potent inhibitors of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteomic-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases. PMID:17559203

Research highlights: {yields} POR1 is a Yarrowia lipolytica ortholog of farA involved in fattyacid response in A. nidulans. {yields} Deletion of POR1 caused growth defects on fattyacids. {yields} {Delta}por1 strain exhibited defects in the induction of genes involved in fattyacid utilization. -- Abstract: The yeast Yarrowia lipolytica effectively utilizes hydrophobic substrates such as fattyacids and n-alkanes. To identify a gene(s) regulating fattyacid utilization in Y. lipolytica, we first studied homologous genes to OAF1 and PIP2 of Saccharomyces cerevisiae, but their disruption did not change growth on oleic acid at all. We next characterized a Y. lipolytica gene, POR1 (primary oleate regulator 1), an ortholog of farA encoding a transcriptional activator that regulates fattyacid utilization in Aspergillus nidulans. The deletion mutant of POR1 was defective in the growth on various fattyacids, but not on glucose, glycerol, or n-hexadecane. It exhibited slight defect on n-decane. The transcriptional induction of genes involved in {beta}-oxidation and peroxisome proliferation by oleate was distinctly diminished in the {Delta}por1 strains. These data suggest that POR1 encodes a transcriptional activator widely regulating fattyacid metabolism in Y. lipolytica.

Objective Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fattyacid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods Ligand-based structure-activity models were used for virtual screening of the Specs database (www.specs.net) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fattyacid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fattyacid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fattyacid synthesis. Implications Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. PMID:24878338

Upregulation of fattyacid synthase (FASN), a key enzyme of de novo lipogenesis, is associated with metastasis in colorectal cancer (CRC). However, the mechanisms of regulation are unknown. Since angiogenesis is crucial for metastasis, we investigated the role of FASN in the neovascularization of CRC. The effect of FASN on tumor vasculature was studied in orthotopic CRCs, the chick embryo chorioallantoic membrane (CAM) and Matrigel plug models using immunohistochemistry, immunofluorescent staining and confocal microscopy. Cell secretion was evaluated by ELISA and antibody arrays. Proliferation, migration and tubulogenesis of endothelial cells (ECs) were assessed in CRC-EC coculture models. In this study, we found that stable knockdown of FASN decreased microvessel density in HT29 and HCT116 orthotopic CRCs and resulted in 'normalization' of tumor vasculature in both orthotopic and CAM models. Furthermore, FASN regulated secretion of pro- and antiangiogenic factors, including vascular endothelial growth factor-A (VEGF-A). Mechanisms associated with the antiangiogenic activity noted with knockdown of FASN included: downregulation of VEGF(189), upregulation of antiangiogenic isoform VEGF(165b) and a decrease in expression and activity of matrix metalloproteinase-9. Furthermore, conditioned medium from FASN knockdown CRC cells inhibited activation of vascular endothelial growth factor receptor-2 and its downstream signaling and decreased proliferation, migration and tubulogenesis of ECs as compared with control medium. Together, these results suggest that cancer cell-associated FASN regulates tumor vasculature through alteration of the profile of secreted angiogenic factors and regulation of their bioavailability. Inhibition of FASN upstream of VEGF-A and other angiogenic pathways can be a novel therapeutic strategy to prevent or inhibit metastasis in CRC. PMID:24510238

Upregulation of fattyacid synthase (FASN), a key enzyme of de novo lipogenesis, is associated with metastasis in colorectal cancer (CRC). However, the mechanisms of regulation are unknown. Since angiogenesis is crucial for metastasis, we investigated the role of FASN in the neovascularization of CRC. The effect of FASN on tumor vasculature was studied in orthotopic CRCs, the chick embryo chorioallantoic membrane (CAM) and Matrigel plug models using immunohistochemistry, immunofluorescent staining and confocal microscopy. Cell secretion was evaluated by ELISA and antibody arrays. Proliferation, migration and tubulogenesis of endothelial cells (ECs) were assessed in CRC–EC coculture models. In this study, we found that stable knockdown of FASN decreased microvessel density in HT29 and HCT116 orthotopic CRCs and resulted in ‘normalization’ of tumor vasculature in both orthotopic and CAM models. Furthermore, FASN regulated secretion of pro- and antiangiogenic factors, including vascular endothelial growth factor-A (VEGF-A). Mechanisms associated with the antiangiogenic activity noted with knockdown of FASN included: downregulation of VEGF189, upregulation of antiangiogenic isoform VEGF165b and a decrease in expression and activity of matrix metalloproteinase-9. Furthermore, conditioned medium from FASN knockdown CRC cells inhibited activation of vascular endothelial growth factor receptor-2 and its downstream signaling and decreased proliferation, migration and tubulogenesis of ECs as compared with control medium. Together, these results suggest that cancer cell-associated FASN regulates tumor vasculature through alteration of the profile of secreted angiogenic factors and regulation of their bioavailability. Inhibition of FASN upstream of VEGF-A and other angiogenic pathways can be a novel therapeutic strategy to prevent or inhibit metastasis in CRC. PMID:24510238

In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fattyacids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative "front-end" desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fattyacid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. PMID:24351909

In order to identify novel genes encoding enzymes involved in the biosynthesis of nutritionally important omega-3 long chain polyunsaturated fattyacids, a database search was carried out in the genomes of the unicellular photoautotrophic green alga Ostreococcus RCC809 and cold-water diatom Fragilariopsis cylindrus. The search led to the identification of two putative “front-end” desaturases (Δ6 and Δ4) from Ostreococcus RCC809 and one Δ6-elongase from F. cylindrus. Heterologous expression of putative open reading frames (ORFs) in yeast revealed that the encoded enzyme activities efficiently convert their respective substrates: 54.1% conversion of α-linolenic acid for Δ6-desaturase, 15.1% conversion of 22:5n-3 for Δ4-desaturase and 38.1% conversion of γ-linolenic acid for Δ6-elongase. The Δ6-desaturase from Ostreococcus RCC809 displays a very strong substrate preference resulting in the predominant synthesis of stearidonic acid (C18:4Δ6,9,12,15). These data confirm the functional characterization of omega-3 long chain polyunsaturated fattyacid biosynthetic genes from these two species which have until now not been investigated for such activities. The identification of these new genes will also serve to expand the repertoire of activities available for metabolically engineering the omega-3 trait in heterologous hosts as well as providing better insights into the synthesis of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in marine microalgae. PMID:24351909

Cystic fibrosis patients and model systems exhibit consistent abnormalities in metabolism of polyunsaturated fattyacids that appear to play a role in disease pathophysiology. Recent in vitro studies have suggested that these changes are due to overexpression of fattyacid desaturases that can be reversed by supplementation with the long-chain polyunsaturated fattyacids docosahexaenoate and eicosapentaenoate. However, these findings have not been tested in vivo. The current study aimed to test these results in an in vivo model system, the CFTR(-/-) knockout mouse. When compared with wild-type mice, the knockout mice exhibited fattyacid abnormalities similar to those seen in cystic fibrosis patients and other model systems. The abnormalities were confined to lung, ileum and pancreas, tissues that are affected by the disease. Similar to in vitro models, these fattyacid changes correlated with increased expression of Δ5- and Δ6-desaturases and elongase 5. Dietary supplementation with high-dose free docosahexaenoate or a combination of lower-dose docosahexaenoate and eicosapentaenoate in triglyceride form corrected the fattyacid abnormalities and reduced expression of the desaturase and elongase genes in the ileum and liver of knockout mice. Only the high-dose docosahexaenoate reduced histologic evidence of disease, reducing mucus accumulation in ileal sections. These results provide in vivo support for the hypothesis that fattyacid abnormalities in cystic fibrosis result from abnormal expression and activity of metabolic enzymes in affected cell types. They further demonstrate that these changes can be reversed by dietary n-3 fattyacid supplementation, highlighting the potential therapeutic benefit for cystic fibrosis patients. PMID:25448610

To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fattyacids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPAR{alpha} agonist and repressed by PPAR{alpha} antagonist. Luciferase reporter gene assays indicated that the CREBH promoter activity was induced by fattyacids and co-expression of PPAR{alpha}. Deletion studies identified the PPRE for PPAR{alpha} activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPAR{alpha} directly binds to the PPRE. Activation of CREBH at fasting through fattyacids and PPAR{alpha} suggest that CREBH is involved in nutritional regulation.

Alkamides and N-acylethanolamines (NAEs) are bioactive, amide-linked lipids that influence plant development. Alkamides are restricted to several families of higher plants and some fungi, whereas NAEs are widespread signaling molecules in both plants and animals. Fattyacid amide hydrolase (FAAH) has been described as a key contributor to NAE hydrolysis; however, no enzyme has been associated with alkamide degradation in plants. Herein reported is synthesis of 12 compounds structurally similar to a naturally occurring alkamide (N-isobutyl-(2E,6Z,8E)decatrienamide or affinin) with different acyl compositions more similar to plant NAEs and various amino alkyl head groups. These "hybrid" synthetic alkamides were tested for activity toward recombinant Arabidopsis FAAH and for their effects on plant development (i.e., cotyledon expansion and primary root length). A substantial increase in FAAH activity was discovered toward NAEs in vitro in the presence of some of these synthetic alkamides, such as N-ethyllauroylamide (4). This "enhancement" effect was found to be due, at least in part, to relief from product inhibition of FAAH by ethanolamine, and not due to an alteration in the oligomerization state of the FAAH enzyme. For several of these alkamides, an inhibition of seedling growth was observed with greater results in FAAH knockouts and less in FAAH over-expressing plants, suggesting that these alkamides could be hydrolyzed by FAAH in planta. The tight regulation of NAE levels in vivo appears to be important for proper seedling establishment, and as such, some of these synthetic alkamides may be useful pharmacological tools to manipulate the effects of NAEs in situ. PMID:25491532

Objective: Accumulating evidence suggests that activation of mouse constitutive androstane receptor (mCAR) alleviates type 2 diabetes and obesity by inhibiting hepatic gluconeogenesis, lipogenesis, and fattyacid synthesis. However, the role of human (h) CAR in energy metabolism is largely unknown. The present study aims to investigate the effects of selective hCAR activators on hepatic energy metabolism in human primary hepatocytes (HPH). Methods: Ligand-based structure–activity models were used for virtual screening of the Specs database ( (www.specs.net)) followed by biological validation in cell-based luciferase assays. The effects of two novel hCAR activators (UM104 and UM145) on hepatic energy metabolism were evaluated in HPH. Results: Real-time PCR and Western blotting analyses reveal that activation of hCAR by UM104 and UM145 significantly repressed the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, two pivotal gluconeogenic enzymes, while exerting negligible effects on the expression of genes associated with lipogenesis and fattyacid synthesis. Functional experiments show that UM104 and UM145 markedly inhibit hepatic synthesis of glucose but not triglycerides in HPH. In contrast, activation of mCAR by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene, a selective mCAR activator, repressed the expression of genes associated with gluconeogenesis, lipogenesis, and fattyacid synthesis in mouse primary hepatocytes, which were consistent with previous observations in mouse model in vivo. Conclusion: Our findings uncover an important species difference between hCAR and mCAR in hepatic energy metabolism, where hCAR selectively inhibits gluconeogenesis without suppressing fattyacid synthesis. Implications: Such species selectivity should be considered when exploring CAR as a potential therapeutic target for metabolic disorders. - Highlights: • Novel hCAR activators were identified by computational and biological approaches. • The role

Omega-3 fattyacids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fattyacids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor alpha (PPAR alpha), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)-treated mice. This occurred via a PPAR alpha-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPAR alpha-deficient mice. Therefore, the beneficial effects of omega-3 fattyacids may be explained by a PPAR alpha-mediated anti-inflammatory effect of oxidized EPA. PMID:12149216

In the present study, supercritical carbon dioxide (SC-CO(2)) extraction of seed oil from winter melon (Benincasa hispida) was investigated. The effects of process variables namely pressure (150-300 bar), temperature (40-50 °C) and dynamic extraction time (60-120 min) on crude extraction yield (CEY) were studied through response surface methodology (RSM). The SC-CO(2) extraction process was modified using ethanol (99.9%) as co-solvent. Perturbation plot revealed the significant effect of all process variables on the CEY. A central composite design (CCD) was used to optimize the process conditions to achieve maximum CEY. The optimum conditions were 244 bar pressure, 46 °C temperature and 97 min dynamic extraction time. Under these optimal conditions, the CEY was predicted to be 176.30 mg-extract/g-dried sample. The validation experiment results agreed with the predicted value. The antioxidant activity and fattyacid composition of crude oil obtained under optimized conditions were determined and compared with published results using Soxhlet extraction (SE) and ultrasound assisted extraction (UAE). It was found that the antioxidant activity of the extract obtained by SC-CO(2) extraction was strongly higher than those obtained by SE and UAE. Identification of fattyacid composition using gas chromatography (GC) showed that all the extracts were rich in unsaturated fattyacids with the most being linoleic acid. In contrast, the amount of saturated fattyacids extracted by SE was higher than that extracted under optimized SC-CO(2) extraction conditions. PMID:23322066

Astrocytes were derived from cortex of two-day-old rat brain and grown in primary culture to confluence. The metabolism of the fattyacids, octanoate and palmitate, to CO{sub 2} in oxidative respiration and to the formation of ketone bodies was examined by radiolabeled tracer methodology. The net production of acetoacetate was also determined by measurement of its mass. The enzymes in the ketogenic pathway were examined by measuring enzymic activity and/or by immunoblot analyses. Labeled CO{sub 2} and labeled ketone bodies were produced from the oxidation of fattyacids labeled at carboxy- and {omega}-terminal carbons, indicating that fattyacids were oxidized by {beta}-oxidation. The results from the radiolabeled tracer studies also indicated that a substantial proportion of the {omega}-terminal 4-carbon unit of the fattyacids bypassed the {beta}-ketothiolase step of the {beta}-oxidation pathway. The ({sup 14}C)acetoacetate formed from the (1-{sup 14}C)labeled fattyacids, obligated to pass through the acetyl-CoA pool, contained 50% of the label at carbon 3 and 50% at carbon 1. In contrast, the ({sup 14}C)acetoacetate formed from the ({omega}-1)labeled fattyacids contained 90% of the label at carbon 3 and 10% at carbon 1.

This study determined and compared the contents of bioactive components in plant seed oils extracted with n-hexane (Soxhlet method) and chloroform/methanol (Folch method) from coriander, caraway, anise, nutmeg and white mustard seeds. Oleic acid dominated among unsaturated fattyacids in nutmeg and anise seed oils while petroselinic acid was present in coriander and caraway oils. Concerning sterols, β-sitosterol was the main component in seed oils extracted with both methods. The content of total phenolics in nutmeg, white mustard and coriander seed oils extracted with chloroform/methanol was higher than in their counterparts prepared with n-hexane. The seed oil samples extracted according to the Folch method exhibited a higher ability to scavenge DPPH radicals compared to the oil samples prepared with the Soxhlet method. DPPH values of the methanolic extracts derived from oils produced with the Folch method were also higher than in the oils extracted with n-hexane. PMID:27451203

Dinoflagellates are prolific producers of polyketide secondary metabolites. Dinoflagellate polyketide synthases (PKSs) have sequence similarity to Type I PKSs, megasynthases that encode all catalytic domains on a single polypeptide. However, in dinoflagellate PKSs identified to date, each catalytic domain resides on a separate transcript, suggesting multiprotein complexes similar to Type II PKSs. Here, we provide evidence through coimmunoprecipitation that single-domain ketosynthase and ketoreductase proteins interact, suggesting a predicted multiprotein complex. In Karenia brevis (C.C. Davis) Gert Hansen & Ø. Moestrup, previously observed chloroplast localization of PKSs suggested that brevetoxin biosynthesis may take place in the chloroplast. Here, we report that PKSs are present in both cytosol and chloroplast. Furthermore, brevetoxin is not present in isolated chloroplasts, raising the question of what chloroplast-localized PKS enzymes might be doing. Antibodies to K. brevis PKSs recognize cytosolic and chloroplast proteins in Ostreopsis cf. ovata Fukuyo, and Coolia monotis Meunier, which produce different suites of polyketide toxins, suggesting that these PKSs may share common pathways. Since PKSs are closely related to fattyacid synthases (FAS), we sought to determine if fattyacid biosynthesis colocalizes with either chloroplast or cytosolic PKSs. [(3) H]acetate labeling showed fattyacids are synthesized in the cytosol, with little incorporation in chloroplasts, consistent with a Type I FAS system. However, although 29 sequences in a K. brevis expressed sequence tag database have similarity (BLASTx e-value <10(-10) ) to PKSs, no transcripts for either Type I (cytosolic) or Type II (chloroplast) FAS are present. Further characterization of the FAS complexes may help to elucidate the functions of the PKS enzymes identified in dinoflagellates. PMID:27007632

In this study, an attempt has been made to synthesize esteramide quat by esterification of palm fattyacids with 1(2-hydroxyethyl piperazine) followed by quaternization with dimethyl sulphate (DMS). The optimum reaction conditions for esterification of palm fattyacids and 1(2-hydroxyethyl piperazine) were found to be 170°C reaction temperature and 150 mmHg pressure. The obtained esteramide was subjected to quaternization with different molar ratios of DMS. The consequences revealed that esteramide to DMS ratio of 1 : 0.95 and duration of quaternization for 2 h yielded esteramide quat of maximum cationic content, i.e., 64.9%. The instrumental analysis, viz. FT-IR, 1H NMR, 13C NMR verified the esterification and subsequent quaternization of the obtained esteramide quat. Furthermore, the surface-active and performance properties of synthesized esteramide quat were also evaluated.

We investigated the viability and fattyacid synthetic activity of in vitro cultured Perkinsus marinus (Dermo) in lipid-free medium and estuarine water, and the infectivity of P. marinus maintained in artificial seawater (ASW). Viability and fattyacid synthetic activity in 7 d old P. marinus meronts maintained in lipid-free medium and estuarine water were tested. The infectivity of meronts incubated in ASW was examined by first incubating P. marinus meronts in ASW for 2, 3 or 7 d, and then inoculating viable ASW-incubated meronts into the shell cavity of individual oysters Crassostrea virginica. P. marinus infection prevalence and intensity in oysters were determined 9 wk post-inoculation. Heavy mortality occurred in meronts maintained in estuarine water, a drop from an initial value of 100% viable to 7.8 and 6.1% after 3 and 14 d incubation, respectively. Viability was 85 and 67% in meronts maintained in lipid-free medium for 3 and 24 d, respectively. Meronts kept in lipid-free medium for 14 d retained their ability to synthesize fattyacids. Viable meronts incubated in ASW remained infective for up to 7 d. The infection prevalences were 85, 48 and 100%, in the treatments inoculated with viable meronts that were incubated in ASW for 2, 3 and 7 d, respectively. Infection prevalence in the group inoculated with viable meronts immediately after they were transferred to ASW ranged from 61 to 85%. Our results suggest that in nature meronts can survive for at least 14 d outside the host. Viable meronts are not only infective, but are also able to replicate and retain their fattyacid synthetic ability for 7 d. PMID:16956060

The de novo fattyacid synthesis catalyzed by key lipogenic enzymes, including fattyacid synthase (FASN) has emerged as one of the novel targets of anti-cancer approaches. The present study explored the possible inhibitory efficacy of [6]-gingerol on de novo fattyacid synthesis associated with mitochondrial-dependent apoptotic induction in HepG2 cells. We observed a dissipation of mitochondrial membrane potential accompanied by a reduction of fattyacid levels. [6]-gingerol administration manifested inhibition of FASN expression, indicating FASN is a major target of [6]-gingerol inducing apoptosis in HepG2 cells. Indeed, we found that increased ROS generation could likely be a mediator of the anti-cancer effect of [6]-gingerol. A reduction of fattyacid levels and induction of apoptosis were restored by inhibition of acetyl-CoA carboxylase (ACC) activity, suggesting an accumulation of malonyl-CoA level could be the major cause of apoptotic induction of [6]-gingerol in HepG2 cells. The present study also showed that depletion of fattyacid following [6]-gingerol treatment caused an inhibitory effect on carnitine palmitoyltransferase-1 activity (CPT-1), whereas C75 augmented CPT-1 activity, indicating that [6]-gingerol exhibits the therapeutic benefit on suppression of fattyacid β-oxidation. PMID:26101700

The de novo fattyacid synthesis catalyzed by key lipogenic enzymes, including fattyacid synthase (FASN) has emerged as one of the novel targets of anti-cancer approaches. The present study explored the possible inhibitory efficacy of [6]-gingerol on de novo fattyacid synthesis associated with mitochondrial-dependent apoptotic induction in HepG2 cells. We observed a dissipation of mitochondrial membrane potential accompanied by a reduction of fattyacid levels. [6]-gingerol administration manifested inhibition of FASN expression, indicating FASN is a major target of [6]-gingerol inducing apoptosis in HepG2 cells. Indeed, we found that increased ROS generation could likely be a mediator of the anti-cancer effect of [6]-gingerol. A reduction of fattyacid levels and induction of apoptosis were restored by inhibition of acetyl-CoA carboxylase (ACC) activity, suggesting an accumulation of malonyl-CoA level could be the major cause of apoptotic induction of [6]-gingerol in HepG2 cells. The present study also showed that depletion of fattyacid following [6]-gingerol treatment caused an inhibitory effect on carnitine palmitoyltransferase-1 activity (CPT-1), whereas C75 augmented CPT-1 activity, indicating that [6]-gingerol exhibits the therapeutic benefit on suppression of fattyacid β-oxidation. PMID:26101700

The relation between fattyacid accumulation, activity of acetyl-CoA carboxylase (ACC), and consequently lipid accumulation was studied in the microalgae Chlorella vulgaris co-immobilized with the plant growth-promoting bacterium Azospirillum brasilense under dark heterotrophic conditions with Na acetate as a carbon source. In C. vulgaris immobilized alone, cultivation experiments for 6 days showed that ACC activity is directly related to fattyacid accumulation, especially in the last 3 days. In co-immobilization experiments, A. brasilense exerted a significant positive effect over ACC activity, increased the quantity in all nine main fattyacids, increased total lipid accumulation in C. vulgaris, and mitigated negative effects of nonoptimal temperature for growth. No correlation between ACC activity and lipid accumulation in the cells was established for three different temperatures. This study demonstrated that the interaction between A. brasilense and C. vulgaris has a significant effect on fattyacid and lipid accumulation in the microalgae. PMID:25129521

The relation between fattyacid accumulation, activity of acetyl-CoA carboxylase (ACC), and consequently lipid accumulation was studied in the microalgae Chlorella vulgaris co-immobilized with the plant growth-promoting bacterium Azospirillum brasilense under dark heterotrophic conditions with Na acetate as a carbon source. In C. vulgaris immobilized alone, cultivation experiments for 6 days showed that ACC activity is directly related to fattyacid accumulation, especially in the last 3 days. In co-immobilization experiments, A. brasilense exerted a significant positive effect over ACC activity, increased the quantity in all nine main fattyacids, increased total lipid accumulation in C. vulgaris, and mitigated negative effects of nonoptimal temperature for growth. No correlation between ACC activity and lipid accumulation in the cells was established for three different temperatures. This study demonstrated that the interaction between A. brasilense and C. vulgaris has a significant effect on fattyacid and lipid accumulation in the microalgae.

Water-in-oil emulsions of metabolizable fattyacid esters, with the non-toxic surfactant Pluronic L122 as emulsifying agent, potentiated the humoral response to bovine serum albumin and staphylococcal toxoid in the mouse. Adjuvant activity was increased by changing the chemical nature of the esters as follows: (i) using a series of ethyl esters, adjuvant activity appeared when the acyl chain length of the fattyacid component was 16 or greater; (ii) isobutyl and isopropyl esters of palmitic acid (C16:0) were superior to ethyl; (iii) the ethyl esters of oleic (C18:1) and linoleic (C18:2) acids were better than stearic (C18:0). Since emulsions prepared with longer chain saturated esters are very viscous or solid at room temperature, and unsaturated esters are chemically reactive, emulsions were prepared with differing proportions of ethyl caprate (C10:0) and butyl stearate. At a ratio of 9:1 the emulsions possessed the low viscosity of ethyl caprate, but gained the adjuvant activity of butyl stearate. 125I-labelled BSA was retained in the footpad to a significantly greater extent than with a caprate emulsion, but reasons are given for believing that slow release of antigen is not the only mechanism of adjuvant activity. The ester emulsions caused more acute but less chronic local inflammation (footpad swelling) than Freund's incomplete adjuvant. PMID:7275184

Diabetes mellitus is often associated with altered fattyacids composition. This study was designed to investigate the role of angiotensin (Ang) (1-7)/Mas receptor in improving fattyacids composition in streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats. Rats treated with STZ (50 mg/kg, i.p. once) developed DN after 8 weeks. Fattyacid composition was estimated in renal cortical tissue by gas chromatography. Treatment with Ang (1-7), A-779, and Ang (1-7) plus A-779 was given from week 4 to week 8. Diabetic rats exhibited a significant increase in levels of saturated fattyacids and a significant decrease in levels of polyunsaturated fattyacids (PUFAs). Treatment with Ang (1-7) significantly attenuated these diabetes-induced changes. In diabetic rats, prior administration of A-779 significantly attenuated the increase in PUFAs produced by Ang (1-7); however, for saturated fattyacids, A-779 significantly blocked the decrease in palmitic acid only. Our study, for the first time, documented that endogenous Ang (1-7) modulates fattyacid composition in rats. Further, treatment with Ang (1-7) significantly attenuated diabetes-induced changes in fattyacids composition. This may be an additional mechanism implying the renoprotective role of Ang (1-7) in diabetic rats.

Targeted engineering of microbial genomes holds much promise for diverse biotechnological applications. Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats/Cas9 systems are capable of efficiently editing microbial genomes, including that of Saccharomyces cerevisiae. Here, we demonstrate the use of TALENs to edit the genome of S. cerevisiae with the aim of inducing the overproduction of fattyacids. Heterodimeric TALENs were designed to simultaneously edit the FAA1 and FAA4 genes encoding acyl-CoA synthetases in S. cerevisiae. Functional yeast double knockouts generated using these TALENs over-produce large amounts of free fattyacids into the cell. This study demonstrates the use of TALENs for targeted engineering of yeast and demonstrates that this technology can be used to stimulate the enhanced production of free fattyacids, which are potential substrates for biofuel production. This proof-of-principle study extends the utility of TALENs as excellent genome editing tools and highlights their potential use for metabolic engineering of yeast and other organisms, such as microalgae and plants, for biofuel production. PMID:25907574

The endoplasmic reticulum quality control protein activating transcription factor 6 (ATF6) has emerged as a novel metabolic regulator. Here, we show that adenovirus-mediated overexpression of the dominant-negative form of ATF6 (dnATF6) increases susceptibility to develop hepatic steatosis in diet-induced insulin-resistant mice and fasted mice. Overexpression of dnATF6 or small interfering RNA-mediated knockdown of ATF6 decreases the transcriptional activity of peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor complex, and inhibits oxygen consumption rates in hepatocytes, possibly through inhibition of the binding of PPARα to the promoter of its target gene. Intriguingly, ATF6 physically interacts with PPARα, enhances the transcriptional activity of PPARα, and triggers activation of PPARα downstream targets, such as CPT1α and MCAD, in hepatocytes. Furthermore, hepatic overexpression of the active form of ATF6 promotes hepatic fattyacid oxidation and protects against hepatic steatosis in diet-induced insulin-resistant mice. These data delineate the mechanism by which ATF6 controls the activity of PPARα and hepatic mitochondria fattyacid oxidation. Therefore, strategies to activate ATF6 could be used as an alternative avenue to improve liver function and treat hepatic steatosis in obesity. PMID:27207533

Δ9-Desaturase (stearoyl-CoA desaturase 1, SCD-1) regulates the desaturation of SFA, mainly stearic and palmitic, to MUFA. Δ6-Desaturase (D6D) and Δ5-desaturase (D5D) are involved in the metabolism of linoleic and α-linolenic acid to polyunsaturated metabolites. The objective of the present study was to study the effects of different types of dietary fat on indices of fattyacid desaturase (FADS) activity (evaluated as product:precursor ratios) in plasma and skeletal muscle in human subjects. A high SCD-1 index has been related to obesity and metabolic disorders, while the D5D index is associated with insulin sensitivity. Fattyacid composition of serum and skeletal muscle lipids was analysed by GLC during a randomised, controlled, 3-month dietary intervention in healthy subjects. A comparison of the effects of a diet containing butter fat (SFA, n 17) with a diet containing monounsaturated fat (MUFA, n 17), keeping all other dietary components constant, showed a reduced SCD-1 activity index by 20% on the MUFA diet compared with the SFA diet assessed in serum cholesteryl esters. The D6D and D5D indices remained unaffected. Supplementation with long-chain n-3 fattyacids reduced the SCD-1 index by a similar magnitude while the D6D index decreased and the D5D index increased. It is concluded that changes in the type of fat in the diet affect the indices of FADS activity in serum and skeletal muscle in human subjects. The desaturase activity indices estimated from the serum lipid ester composition are significantly related to corresponding indices studied in skeletal muscle phospholipids. PMID:23414551

In recent years, oxidative stress has been implicated in the pathophysiology of a large number of diseases or disorders which are initiated and/or exacerbated by pro-oxidants such as various drugs including alcohol and food additives. The present study was carried out to evaluate the effects of oral treatment with polyherbal formulation Normeta (2 ml and 4 ml/kg) on hepatic damage induced by alcohol 10-30% (blood alcohol was maintained at levels between 150 and 350 mg/dl), thermally oxidized oil (polyunsaturated fattyacids) (15% of diet) and carbonyl iron (1.5-2% of diet) for 30 days in rats. In vitro studies with 1, 1-Diphenyl, 2-Picrylhydrazyl (DPPH), Nitric oxide and Ferric chloride (Fe(+3) ions) showed that Normeta possesses antioxidant and metal chelating activity. Alcohol, polyunsaturated fattyacids and iron feeding produced an increase in serum levels of iron, serum glutamate pyruvate transaminase and decrease in serum proteins. It was also associated with elevated lipid peroxidation (thiobarbituric acid reactive substances) and disruption of antioxidant defence mechanism in liver, decreased body weight and increased liver to body weight ratio. Oral administration of Normeta along with alcohol, polyunsaturated fattyacids and iron decreased the serum iron, serum glutamate pyruvate transaminase levels and increased serum protein levels. The levels of liver thiobarbituric acid reactive substances were decreased and the activities of antioxidant enzymes superoxide dismutase and catalase were increased. Improvement in body weight and liver to body weight ratio was also observed. The effects of Normeta on physico-metabolic parameters were comparable with silymarin. This indicates that Normeta has favourable effect in bringing down the severity of hepatotoxicity. PMID:19486336

The essential oil compound, fattyacid composition and the in vitro antioxidant activity of the root and aerial of Glycyrrhiza echinata L., a medicinal plant growing in Turkey, have been studied. The antioxidant capacity tests were designed to evaluate the antioxidant activities of methanol extracts. Total phenolic and flavonoid concentrations of each extract were also determined by using both Folin-Ciocalteu reagent and aluminum chloride. The aerial part was found to possess the highest total phenolic content (146.30 ± 4.58 mg GAE/g) and total antioxidant capacity (175.33 ± 3.98 mg AE/g). The essential oil from root and aerial parts was analyzed by gas chromatography mass spectroscopy (GC-MS) systems. The major components identified were n-hexadecanoic acid, hexahydro farnesyl acetone, α-caryophyllen, hexanal and phytol. In fattyacid profiles of plant, palmitic, stearic, oleic and linoleic acid were detected as the main components. The results of this study have shown that the extracts G. echinata are suitable as a natural antioxidant and food supplement source for pharmacological and food industries due to their beneficial chemical composition and antioxidant capacity. PMID:27418901

ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fattyacid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fattyacid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fattyacid biosynthesis, were enhanced in rats fed EPL diet. The increased fattyacid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fattyacid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

ɛ-Polylysine (EPL) is used as a natural preservative in food. However, few studies have been conducted to assess the beneficial functions of dietary EPL. The purpose of this study was to elucidate the mechanism underlying the inhibition of neutral and acidic sterol absorption and hepatic enzyme activity-related fattyacid biosynthesis following EPL intake. EPL digest prepared using an in vitro digestion model had lower lipase activity and micellar lipid solubility and higher bile acid binding capacity than casein digest. Male Wistar rats were fed an AIN-93G diet containing 1% (wt/wt) EPL or l-lysine. After 4 weeks of feeding these diets, the marked decrease in serum and liver triacylglycerol contents by the EPL diet was partly attributed to increased fecal fattyacid excretion. The activities of hepatic acetyl-coenzyme A carboxylase and glucose-6-phosphate dehydrogenase, which are key enzymes of fattyacid biosynthesis, were enhanced in rats fed EPL diet. The increased fattyacid biosynthesis activity due to dietary EPL may be prevented by the enhancement of fecal fattyacid excretion. The hypocholesterolemic effect of EPL was mediated by increased fecal neutral and acidic sterol excretions due to the EPL digest suppressing micellar lipid solubility and high bile acid binding capacity. These results show that dietary EPL has beneficial effects that could help prevent lifestyle-related diseases such as hyperlipidemia and atherosclerosis. PMID:25866749

This study represents the first report on the chemical composition and biological activity of Trifolium angustifolium var. angustifolium. The major components of the essential oil were identified as hexatriacontene (23.0%), arachidic acid (15.5%) and α-selinene (10.0%). The main constituents of the fattyacid obtained from the petroleum ether extract were identified as palmitic acid (29.8%), linoleic acid (18.6%) and oleic acid (10.5%). In particular, the water extract exhibited higher activity than α-tocopherol and BHT, which were used as standards in the ABTS cation radical scavenging assay and indicated higher inhibitory effect against acetylcholinesterase enzyme than the reference compound, galanthamine but exhibited weak activity in β-carotene bleaching, DPPH-free radical scavenging, and cupric-reducing antioxidant capacity assays. The petroleum ether extract exhibited higher activity than α-tocopherol which was used as standard in the β-carotene bleaching method at concentration 100 μg/mL. The acetone extract exhibited higher activity than α-tocopherol which was used as standard cupric reducing antioxidant capacity (CUPRAC) method at 100 μg/mL concentration. The acetone and methanol extracts were active on all microorganisms tested with a small zone diameter indicating weak activity. PMID:25561929

There is growing evidence that the role of lipids in innate immunity is more important than previously realized. How lipids interact with bacteria to achieve a level of protection, however, is still poorly understood. To begin to address the mechanisms of antibacterial activity, we determined MICs and minimum bactericidal concentrations (MBCs) of lipids common to the skin and oral cavity—the sphingoid bases d-sphingosine, phytosphingosine, and dihydrosphingosine and the fattyacids sapienic acid and lauric acid—against four Gram-negative bacteria and seven Gram-positive bacteria. Exact Kruskal-Wallis tests of these values showed differences among lipid treatments (P < 0.0001) for each bacterial species except Serratia marcescens and Pseudomonas aeruginosa. d-Sphingosine (MBC range, 0.3 to 19.6 μg/ml), dihydrosphingosine (MBC range, 0.6 to 39.1 μg/ml), and phytosphingosine (MBC range, 3.3 to 62.5 μg/ml) were active against all bacteria except S. marcescens and P. aeruginosa (MBC > 500 μg/ml). Sapienic acid (MBC range, 31.3 to 375.0 μg/ml) was active against Streptococcus sanguinis, Streptococcus mitis, and Fusobacterium nucleatum but not active against Escherichia coli, Staphylococcus aureus, S. marcescens, P. aeruginosa, Corynebacterium bovis, Corynebacterium striatum, and Corynebacterium jeikeium (MBC > 500 μg/ml). Lauric acid (MBC range, 6.8 to 375.0 μg/ml) was active against all bacteria except E. coli, S. marcescens, and P. aeruginosa (MBC > 500 μg/ml). Complete killing was achieved as early as 0.5 h for some lipids but took as long as 24 h for others. Hence, sphingoid bases and fattyacids have different antibacterial activities and may have potential for prophylactic or therapeutic intervention in infection. PMID:22155833

The agar diffusion assay was used to examine antibacterial activity of alkaline salts of caproic, caprylic, capric, lauric, and myristic acids. A 0.5M concentration of each fattyacid was dissolved in 1.0 M potassium hydroxide (KOH), and pH of the mixtures was adjusted to 10.5 with citric acid. Solu...

Muscle contraction increases glucose uptake and fattyacid (FA) metabolism in isolated rat skeletal muscle, due at least in part to an increase in AMP-activated kinase activity (AMPK). However, the extent to which AMPK plays a role in the regulation of substrate utilization during contraction is not fully understood. We examined the acute effects of 5-aminoimidazole-4-carboxamide riboside (AICAR; 2 mm), a pharmacological activator of AMPK, on FA metabolism and glucose oxidation during high intensity tetanic contraction in isolated rat soleus muscle strips. Muscle strips were exposed to two different FA concentrations (low fattyacid, LFA, 0.2 mm; high fattyacid, HFA, 1 mm) to examine the role that FA availability may play in both exogenous and endogenous FA metabolism with contraction and AICAR. Synergistic increases in AMPK α2 activity (+45%; P < 0.05) were observed after 30 min of contraction with AICAR, which further increased exogenous FA oxidation (LFA: +71%, P < 0.05; HFA: +46%, P < 0.05) regardless of FA availability. While there were no changes in triacylglycerol (TAG) esterification, AICAR did increase the ratio of FA partitioned to oxidation relative to TAG esterification (LFA: +65%, P < 0.05). AICAR significantly blunted endogenous TAG hydrolysis (LFA: −294%, P < 0.001; HFA: −117%, P < 0.05), but had no effect on endogenous oxidation rates, suggesting a better matching between TAG hydrolysis and subsequent oxidative needs of the muscle. There was no effect of AICAR on the already elevated rates of glucose oxidation during contraction. These results suggest that FA metabolism is very sensitive to AMPK α2 stimulation during contraction. PMID:15774529

It is increasingly understood that in the aging brain, especially in the case of patients suffering from neurodegenerative diseases, some fattyacids at pathologically high concentrations exert detrimental activities. To study such activities, we here analyze genetic diseases, which are due to compromised metabolism of specific fattyacids, either the branched-chain phytanic acid or very long-chain fattyacids (VLCFAs). Micromolar concentrations of phytanic acid or of VLCFAs disturb the integrity of neural cells by impairing Ca2+ homeostasis, enhancing oxidative stress or de-energizing mitochondria. Finally, these combined harmful activities accelerate cell death. Mitochondria are more severely targeted by phytanic acid than by VLCFAs. The insertion of VLCFAs into the inner membrane distorts the arrangement of membrane constituents and their functional interactions. Phytanic acid exerts specific protonophoric activity, induces reactive oxygen species (ROS) generation, and reduces ATP generation. A clear inhibition of the Na+, K+-ATPase activity by phytanic acid has also been reported. In addition to the instantaneous effects, a chronic exposure of brain cells to low micromolar concentrations of phytanic acid may produce neuronal damage in Refsum disease by altering epigenetic transcriptional regulation. Myelin-producing oligodendrocytes respond with particular sensitivity to VLCFAs. Deleterious activity of VLCFAs on energy-dependent mitochondrial functions declines with increasing the hydrocarbon chain length (C22:0 > C24:0 > C26:0). In contrast, the reverse sequence holds true for cell death induction by VLCFAs (C22:0 < C24:0 < C26:0). In adrenoleukodystrophy, the uptake of VLCFAs by peroxisomes is impaired by defects of the ABCD1 transporter. Studying mitochondria from ABCD1-deficient and wild-type mice proves that the energy-dependent functions are not altered in the disease model. Thus, a defective ABCD1 apparently exerts no obvious adaptive pressure on

Background The recent escalation of US Military suicide deaths to record numbers has been an sentinel for impaired force efficacy and has accelerated the search for reversible risk factors. Objective Determine if deficiencies of neuroactive highly unsaturated omega-3 essential fattyacids (n-3 HUFA), in particular docosahexaenoic acid (DHA), are associated with increased risk of suicide death among a large random sample of active duty US military. Methods Serum fattyacids were quantified as % of total fattyacids, among US military suicide deaths (n= 800) and controls (n=800) matched for age, date of collection, sex, rank and year of incident. Participants were Active Duty US Military personnel (2002–2008). Outcome measures, included death by suicide, post deployment health assessment questionnaire and ICD-9 mental health diagnosis data. Results Risks of suicide death was 14% higher, per standard deviation [SD] lower DHA % (OR =1.14, 95% CI; 1.02–1.27, p<0.03), in adjusted logistic regressions. Among men risk of suicide death was 62% greater with low serum DHA status (adjusted Odds Ratio [OR] =1.62, 95% CI 1.12–2.34, p<0.01, comparing DHA below 1.75% [n=1,389] to above [n=141]). Risk of suicide death was 54% greater in those who reported having seen wounded, dead or killed coalition personnel (OR = 1.54, 95% CI; 1.12–2.12, p< 0.007.) Conclusion This US military population had a very low and narrow range of n-3 HUFA status. Although these data suggest that low serum DHA may be a risk factor for suicides, well designed intervention trials are needed to evaluate causality. PMID:21903029

Aim: Defects in fattyacid metabolism contribute to the pathogenesis of insulin resistance and obesity. In this study, we investigated the effects of a novel compound yhhu981 on fattyacid metabolism in vitro and in vivo. Methods: The capacity to stimulate fattyacid oxidation was assessed in C2C12 myotubes. The fattyacid synthesis was studied in HepG2 cells using isotope tracing. The phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) was examined with Western blot analysis. For in vivo experiments, ob/ob mice were orally treated with yhhu981 acutely (300 mg/kg) or chronically (150 or 300 mg·kg−1·d−1 for 22 d). On the last day of treatment, serum and tissue samples were collected for analysis. Results: Yhhu981 (12.5–25 μmol/L) significantly increased fattyacid oxidation and the expression of related genes (Sirt1, Pgc1α and Mcad) in C2C12 myotubes, and inhibited fattyacid synthesis in HepG2 cells. Furthermore, yhhu981 dose-dependently increased the phosphorylation of AMPK and ACC in both C2C12 myotubes and HepG2 cells. Compound C, an AMPK inhibitor, blocked fattyacid oxidation in yhhu981-treated C2C12 myotubes and fattyacid synthesis decrease in yhhu981-treated HepG2 cells. Acute administration of yhhu981 decreased the respiratory exchange ratio in ob/ob mice, whereas chronic treatment with yhhu981 ameliorated the lipid abnormalities and ectopic lipid deposition in skeletal muscle and liver of ob/ob mice. Conclusion: Yhhu981 is a potent compound that stimulates fattyacid oxidation, and exerts pleiotropic effects on lipid metabolism by activating AMPK. PMID:25732571

Mammalian spermatozoa are characterized by a high proportion of polyunsaturated fattyacids (PUFA) which play a crucial role in fertilization. This review focuses on analysis of sperm fattyacid profiles and the effects of omega-3, saturated and trans dietary and sperm fattyacids on sperm parameters. Two major points have been pivotal points of investigation in the field of sperm fattyacid profiles: first, the comparison between fattyacid profiles of fertile and infertile men and second, the effect of dietary fattyacids on sperm fattyacid profiles as well as sperm quality and quantity. Docosahexaenoic acid (DHA, C22:6n-3), and palmitic acid (C16:0) are the predominant PUFA and saturated fattyacids, respectively, in human sperm cells. Higher levels of DHA are concentrated on the sperm's head or tail varying among different species. However, the human sperm head contains a higher concentration of DHA. Dietary fattyacids influence on sperm fattyacid profiles and it seems that sperm fattyacid profiles are most sensitive to dietary omega-3 PUFA. Although improvements in sperm parameters are a response to omega-3 sources after more than 4 weeks of supplementation in the male diet, time-dependent and dose-dependent responses may explain the failure in some experiments. In human spermatozoa, elevated saturated or trans fattyacid concentration and a low DHA level is a concern. The regulations of the sperm fattyacid mean melting point as well as expression regulation of peroxisome proliferator-activated receptor gamma (PPARG) alongside with spermatozoon assembly, anti-apoptosis effects, eicosanoid formation, and hormone activity are the putative key factors that induce a response by inclusion of omega-3 PUFA. PMID:25951427

Accumulating evidence in animals and humans shows that dietary fattyacids influence the absorption and utilization of certain mineral elements. Fat intake exceeding 10% of energy intake reduces calcium uptake and use by the body, and this effect is more pronounced with saturated compared to unsatu...

A simple, highly specific, and sensitive bioluminescent method for determination of free fattyacids in unextracted plasma or serum has been developed. The method is based on the activation of free fattyacids by acyl-CoA synthetase (EC 6.2.1.3). The pyrophosphate formed is used to phosphorylate fructose 6-phosphate in a reaction catalyzed by the enzyme pyrophosphate-fructose-6-phosphate phosphotransferase (EC 4.1.2.13). The triosephosphates produced from fructose 1,6-bisphosphate by aldolase are oxidized by NAD in the presence of arsenate to 3-phosphoglycerate. The NADH is detected via the bacterial NADH-linked luciferase system. Excellent agreement has been obtained by comparison with accepted methods. In addition, for the determination of serum free fattyacids, the method is particularly applicable for following lipolysis of isolated adipocytes. PMID:6486422

Albumin-bound fattyacids is the main cause of renal damage, PPARα is responsible in the metabolism of fattyacids. Previous study found that PPARα played a protective role in fattyacids overload associated tubular injury. The aim of the present study is to investigate whether fenofibrate, a PPARα ligands, could contribute to the renoprotective action in fattyacids overload proximal tubule epithelial cells. We observed in HK-2 cells that fenofibrate significantly inhibited fattyacids bound albumin (FA-BSA) induced up-regulation of MCP-1 and IL-8. Treatment with fenofibrate attenuated renal oxidative stress induced by FA-BSA as evidenced by decreased MDA level, increased SOD activity and catalase, GPx-1 expression. FA-BSA induced apoptosis of HK-2 cells were also obviously prevented by fenofibrate. Furthermore, fenofibrate significantly increased the expression of PPARα mRNA and protein in FA-BSA treated cells. Finally, the activation of NF-kB induced by FA-BSA was markedly suppressed by fenofibrate. Taken together, our study describes a renoprotective role of fenofibrate in fattyacids associated tubular toxicity, and the transcriptional activation of PPARα and suppression of NF-kB were at least partially involved. PMID:26617775

Albumin-bound fattyacids is the main cause of renal damage, PPARα is responsible in the metabolism of fattyacids. Previous study found that PPARα played a protective role in fattyacids overload associated tubular injury. The aim of the present study is to investigate whether fenofibrate, a PPARα ligands, could contribute to the renoprotective action in fattyacids overload proximal tubule epithelial cells. We observed in HK-2 cells that fenofibrate significantly inhibited fattyacids bound albumin (FA-BSA) induced up-regulation of MCP-1 and IL-8. Treatment with fenofibrate attenuated renal oxidative stress induced by FA-BSA as evidenced by decreased MDA level, increased SOD activity and catalase, GPx-1 expression. FA-BSA induced apoptosis of HK-2 cells were also obviously prevented by fenofibrate. Furthermore, fenofibrate significantly increased the expression of PPARα mRNA and protein in FA-BSA treated cells. Finally, the activation of NF-kB induced by FA-BSA was markedly suppressed by fenofibrate. Taken together, our study describes a renoprotective role of fenofibrate in fattyacids associated tubular toxicity, and the transcriptional activation of PPARα and suppression of NF-kB were at least partially involved. PMID:26617775

Effects of fattyacids on human neutrophil-mediated killing of Plasmodium falciparum asexual blood forms were investigated by using a quantitative radiometric assay. The results showed that the antiparasitic activity of neutrophils can be greatly increased (>threefold) by short-term treatment with fattyacids with 20 to 24 carbon atoms and at least three double bonds. In particular, the n-3 polyenoic fattyacids, eicosapentaenoic and docosahexaenoic acids, and the n-6 fattyacid, arachidonic acid, significantly enhanced neutrophil antiparasitic activity. This effect was >1.5-fold higher than that induced by an optical concentration of the known agonist cytokine tumor necrosis factor alpha (TNF-alpha). At suboptimal concentrations, the combination of arachidonic acid and TNF-alpha caused a synergistic increase in neutrophil-mediated parasite killing. The fattyacid-induced effect was independent of the availability of serum opsonins but dependent on the structure of the fattyacids. The length of the carbon chain, degree of unsaturation, and availability of a free carboxyl group were important determinants of fattyacidactivity. The fattyacids which increased neutrophil-mediated killing primed the enhanced superoxide radical generation of neutrophils in response to P. falciparum as detected by chemiluminescence. Scavengers of oxygen radicals significantly reduced the fattyacid-enhanced parasite killing, but cyclooxygenase and lipoxygenase inhibitors had no effect. These findings have identified a new class of immunoenhancers that could be exploited to increase resistance against Plasmodium species. PMID:9317021

The origin of the fattyacidactivation and formaldehyde dehydrogenase activity that distinguishes human class III alcohol dehydrogenase (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) from all other alcohol dehydrogenases has been examined by site-directed mutagenesis of its Arg-115 residue. The Ala- and Asp-115 mutant proteins were expressed in Escherichia coli and purified by affinity chromatography and ion-exchange HPLC. The activities of the recombinant native and mutant enzymes toward ethanol are essentially identical, but mutagenesis greatly decreases the kcat/Km values for glutathione-dependent formaldehyde oxidation. The catalytic efficiency for the Asp variant is < 0.1% that of the unmutated enzyme, due to both a higher Km and a lower kcat value. As with the native enzyme, neither mutant can oxidize methanol, be saturated by ethanol, or be inhibited by 4-methylpyrazole; i.e., they retain these class III characteristics. In contrast, however, their activation by fattyacids, another characteristic unique to class III alcohol dehydrogenase, is markedly attenuated. The Ala mutant is activated only slightly, but the Asp mutant is not activated at all. The results strongly indicate that Arg-115 in class III alcohol dehydrogenase is a component of the binding site for activatingfattyacids and is critical for the binding of S-hydroxymethylglutathione in glutathione-dependent formaldehyde dehydrogenase activity. PMID:8460164

Inspired by the anti-human immunodeficiency virus (HIV) activity of analogues of β-galactosylceramide (GalCer), a set of mono- and di- saccharide fattyacid esters were designed as GalCer mimetics and their binding to the V3 loop peptide of HIV-1 and anti-HIV activity evaluated. 1,1-linked Gal-Man and Glu-Man disaccharides with an ester on the Man subunit bound the V3 loop peptide and inhibited HIV infectivity in single round infection assays with the TZM-bl cell line. IC50's were in the 50 μM range with no toxicity to the cells at concentrations up to 200 μM. These compounds appear to inhibit virus entry at early steps in viral infection since they were inactive if added post viral entry. Although these compounds were found to bind to the V3 loop peptide of gp120, it is not clear that this interaction is responsible for their anti-HIV activity because the relative binding affinity of closely related analogues did not correlate with their antiviral behavior. The low cytotoxicity of these 1,1-linked disaccharide fattyacid esters, combined with the easy accessibility to structurally diverse analogues make these molecules attractive leads for new topical anti-viral agents. PMID:21783371

The present invention relates to the identification of nucleic acid sequences and constructs, and methods related thereto, and the use of these sequences and constructs to produce genetically modified plants for the purpose of altering the composition of plant oils, waxes and related compounds.

Phosphorylation of proteins by Ser/Thr protein kinases (STPKs) has recently become of major physiological importance because of its possible involvement in virulence of bacterial pathogens. Although Mycobacterium tuberculosis has eleven STPKs, the nature and function of the substrates of these enzymes remain largely unknown. In this work, we have identified for the first time STPK substrates in M. tuberculosis forming part of the type II fattyacid synthase (FAS-II) system involved in mycolic acid biosynthesis: the malonyl-CoA::AcpM transacylase mtFabD, and the beta-ketoacyl AcpM synthases KasA and KasB. All three enzymes were phosphorylated in vitro by different kinases, suggesting a complex network of interactions between STPKs and these substrates. In addition, both KasA and KasB were efficiently phosphorylated in M. bovis BCG each at different sites and could be dephosphorylated by the M. tuberculosis Ser/Thr phosphatase PstP. Enzymatic studies revealed that, whereas phosphorylation decreases the activity of KasA in the elongation process of long chain fattyacids synthesis, this modification enhances that of KasB. Such a differential effect of phosphorylation may represent an unusual mechanism of FAS-II system regulation, allowing pathogenic mycobacteria to produce full-length mycolates, which are required for adaptation and intracellular survival in macrophages. PMID:16873379

The composition of the fattyacids of the roots and aerial parts of Aritolochia longa (Aristolacheae) and Bryonia dioïca (Cucurbutaceae) was analyzed by gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The oils extracted from the aerial parts of both species were rich in polyunsaturated fattyacids with the essential linolenic and linoleic acids being the most prominent compounds. Oleic and linoleic acids were the majors fattyacids in the roots of both species. Whatever the plant part analyzed and the species, the saturated fattyacids were predominantly composed of palmitic and stearic acids. The antibacterial activity, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the lipid extracts were determined against a panel of five bacterial strains. The results showed that the sensitivity to the lipid extracts was different for the test bacterial strains, and the susceptibility of gram positive bacteria was found to be greater than gram negative bacteria. The antibacterial activity of the root lipid extracts was particularly important against Enterococcus feacium (CMI value of 125 µg/mL; CMB values > 250 µg/mL) and Streptococcus agalactiae (CMI value of 125 µg/mL; CMB values 250 µg/mL for A. longa roots). These results indicate that A. longa and B. dioïca could be considered as good sources of essential fattyacids which can act as natural antibacterial agents. PMID:27430383

In insects, epoxide hydrolases (EHs) play critical roles in the metabolism of xenobiotic epoxides from the food resources and in the regulation of endogenous chemical mediators, such as juvenile hormones. Using the baculovirus expression system, we expressed and characterized an epoxide hydrolase from Anopheles gambiae (AgEH) that is distinct in evolutionary history from insect juvenile hormone epoxide hydrolases (JHEHs). We partially purified the enzyme by ion exchange chromatography and isoelectric focusing. The experimentally determined molecular weight and pI were estimated to be 35kD and 6.3 respectively, different than the theoretical ones. The AgEH had the greatest activity on long chain epoxy fattyacids such as 14,15-epoxyeicosatrienoic acids (14,15-EET) and 9,10-epoxy-12Z-octadecenoic acids (9,10-EpOME or leukotoxin) among the substrates evaluated. Juvenile hormone III, a terpenoid insect growth regulator, was the next best substrate tested. The AgEH showed kinetics comparable to the mammalian soluble epoxide hydrolases, and the activity could be inhibited by AUDA [12-(3-adamantan-1-yl-ureido) dodecanoic acid], a urea-based inhibitor designed to inhibit the mammalian soluble epoxide hydrolases. The rabbit serum generated against the soluble epoxide hydrolase of Mus musculus can both cross-react with natural and denatured forms of the AgEH, suggesting immunologically they are similar. The study suggests there are mammalian sEH homologs in insects, and epoxy fattyacids may be important chemical mediators in insects. PMID:25173592

Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fattyacids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fattyacid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies. PMID:24478369

The intestinal mucosa is characterized by a high complexity in terms of structure and functions and allows for a controlled demarcation towards the gut lumen. On the one hand it is responsible for pulping and selective absorption of alimentary substances ensuring the immunological tolerance, on the other hand it prevents the penetration of micro-organisms as well as bacterial outgrowth. The continuous regeneration of surface epithelia along the crypt-villus-axis in the small intestine is crucial to assuring these various functions. The core phenomena of intestinal epithelia regeneration comprise cell proliferation, migration, differentiation, and apoptosis. These partly contrarily oriented processes are molecularly balanced through numerous interacting signaling pathways like Wnt/β-catenin, Notch and Hedgehog, and regulated by various modifying factors. One of these modifiers is acyl-CoA synthetase 5 (ACSL5). It plays a key role in de novo lipid synthesis, fattyacid degradation and membrane modifications, and regulates several intestinal processes, primarily through different variants of protein lipidation, e.g., palmitoylation. ACSL5 was shown to interact with proapoptotic molecules, and besides seems to inhibit proliferation along the crypt-villus-axis. Because of its proapoptotic and antiproliferative characteristics it could be of significant relevance for intestinal homeostasis, cellular disorder and tumor development. PMID:24259967

Nitrated fattyacids are the product of nitrogen dioxide reaction with unsaturated fattyacids. The discovery of peroxynitrite and peroxidase-induced nitration of biomolecules led to the initial reports of endogenous nitrated fattyacids. These species increase during ischemia reperfusion, but concentrations are often at or near the limits of detection. Here, we describe multiple methods for nitrated fattyacid synthesis, sample extraction from complex biological matrices, and a rigorous method of qualitative and quantitative detection of nitrated fattyacids by LC-MS. In addition, optimized instrument conditions and caveats regarding data interpretation are discussed. PMID:23200809

This paper focused on the effects of waste activated sludge (WAS) and surfactant sodium dodecylbenzene sulfonate (SDBS) addition on primary sludge (PS) hydrolysis and short-chain fattyacids (SCFA) accumulation in fermentation. The results showed that sludge hydrolysis, SCFA accumulation, NH(4)(+)-N and PO(4)(3-)-P release, and volatile suspended solids (VSS) reduction were increased by WAS addition to PS, which were further increased by the addition of SDBS to the mixture of PS and WAS. Acetic, propionic and valeric acids were the top three SCFA in all experiments. Also, the fermentation liquids of PS, PS+WAS, and PS+WAS+SDBS were added, respectively, to municipal wastewater to examine their effects on biological municipal wastewater treatment, and the enhancement of both wastewater nitrogen and phosphorus removals was observed compared with no fermentation liquid addition. PMID:20096564

Radiolabeled long-chain fattyacids have diagnostic value as radiopharmaceutical tools in myocardial imaging. Some applications of these fattyacids are limited due to their natural metabolic degradation in vivo with subsequent washout of the radioactivity from the myocardium. The identification of structural features that will increase the myocardial residence time without decreasing the heart uptake of long-chain fattyacids is of interest. Fattyacids containing the tellurium heteroatom were the first modified fattyacids developed that show unique prolonged myocardial retention and low blood levels. Our detailed studies with radioiodinated vinyliodide substituted tellurium fattyacids demonstrate that heart uptake is a function of the tellurium position. New techniques of tellurium and organoborane chemistry have been developed for the synthesis of a variety of radioiodinated iodoalkenyl tellurium fattyacids. 9 refs., 3 figs., 2 tabs.

Long-chain fattyacids are natural uncouplers of oxidative phosphorylation in mitochondria. The protonophoric mechanism of this action is due to transbilayer movement of undissociated fattyacid in one direction and the passage of its anion in the opposite direction. The transfer of the dissociated form of fattyacid can be, at least in some kinds of mitochondrion, facilitated by adenine nucleotide translocase. Apart from dissipating the electrochemical proton gradient, long-chain fattyacids decrease the activity of the respiratory chain by mechanism(s) not fully understood. In intact cells and tissues fattyacids operate mostly as excellent respiratory substrates, providing electrons to the respiratory chain. This function masks their potential uncoupling effect which becomes apparent only under special physiological or pathological conditions characterized by unusual fattyacid accumulation. Short- and medium-chain fattyacids do not have protonophoric properties. Nevertheless, they contribute to energy dissipation because of slow intramitochondrial hydrolysis of their activation products, acyl-AMP and acyl-CoA. Long-chain fattyacids increase permeability of mitochondrial membranes to alkali metal cations. This is due to their ionophoric mechanism of action. Regulatory function of fattyacids with respect to specific cation channels has been postulated for the plasma membrane of muscle cells, but not demonstrated in mitochondria. Under cold stress, cold acclimation and arousal from hibernation the uncoupling effect of fattyacids may contribute to increased thermogenesis, especially in the muscle tissue. In brown adipose tissue, the special thermogenic organ of mammals, long-chain fattyacids promote operation of the unique natural uncoupling protein, thermogenin. As anionic amphiphiles, long-chain fattyacids increase the negative surface charge of biomembranes, thus interfering in their enzymic and transporting functions. PMID:8399375

Immobilization of lipase MAS1 from marine Streptomyces sp. strain W007 and its application in catalyzing esterification of n-3 polyunsaturated fattyacids (PUFA) with glycerol were investigated. The resin XAD1180 was selected as a suitable support for the immobilization of lipase MAS1, and its absorption ability was 75mg/g (lipase/resin ratio) with initial buffer pH value of 8.0. The thermal stability of immobilized MAS1 was improved significantly compared with that of the free lipase. Immobilized MAS1 had no regiospecificity in the hydrolysis of triolein. The highest esterification degree (99.31%) and TAG content (92.26%) by immobilized MAS1-catalyzed esterification were achieved under the optimized conditions, which were significantly better than those (82.16% and 47.26%, respectively) by Novozym 435. More than 92% n-3 PUFA was incorporated into TAG that had similar fattyacids composition to the substrate (n-3 PUFA). The immobilized MAS1 exhibited 50% of its initial activity after being used for five cycles. PMID:27596418

We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fattyacid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fattyacid opens the way for new formulations with a complex structure without the addition of any extra compound. PMID:27241163

Fructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fattyacid synthesis and inhibition of fattyacid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fattyacid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25mM for 24h. The expression and activity of the enzymes and transcription factors relating to fattyacid β-oxidation were evaluated. Fructose inhibited the activity of fattyacid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fattyacid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation. PMID:24434080

Fattyacid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fattyacid binding protein with high affinity for a variety of long chain fattyacids isolated from rat heart myocytes. It is proposed that this endothelial membrane fattyacid binding protein might mediate the myocardial uptake of fattyacids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fattyacids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fattyacid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fattyacid influx rate is saturable by increasing fattyacid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fattyacid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fattyacid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fattyacid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 {plus minus} 0.024 mumol/g and 0.37 {plus minus} 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fattyacids with the 40-kDa membrane fattyacid binding protein of cardiac endothelial cells.

Aberrant NOTCH1 signalling is critically involved in multiple models of colorectal cancer (CRC) and a prominent role of NOTCH1 activity during inflammation has emerged. Epithelial to Mesenchymal Transition (EMT), a crucial event promoting malignant transformation, is regulated by inflammation and Metalloproteinase-9 (MMP9) plays an important role in this process. Eicosapentaenoic Acid (EPA), an omega-3 polyunsaturated fattyacid, was shown to prevent colonic tumors in different settings. We recently found that an extra-pure formulation of EPA as Free FattyAcid (EPA-FFA) protects from colon cancer development in a mouse model of Colitis-Associated Cancer (CAC) through modulation of NOTCH1 signalling. In this study, we exposed colon cancer cells to an inflammatory stimulus represented by a cytokine-enriched Conditioned Medium (CM), obtained from THP1-differentiated macrophages. We found, for the first time, that CM strongly up-regulated NOTCH1 signalling and EMT markers, leading to increased invasiveness. Importantly, NOTCH1 signalling was dependent on MMP9 activity, upon CM exposure. We show that a non-cytotoxic pre-treatment with EPA-FFA antagonizes the effect of inflammation on NOTCH1 signalling, with reduction of MMP9 activity and invasiveness. In conclusion, our data suggest that, in CRC cells, inflammation induces NOTCH1 activity through MMP9 up-regulation and that this mechanism can be counteracted by EPA-FFA. PMID:26864323

Fattyacid biosynthesis from (1-{sup 14}C)acetate was optimized in plastids isolated from primary root tips of 7-day-old germinating pea seeds. Fattyacid synthesis was maximum at approximately 80 nmoles/hr/mg protein in the presence of 200 {mu}M acetate, 0.5 mM each of NADH, NADPH and CoA, 6 mM each of ATP and MgCl{sub 2}, 1 mM each of the MnCl{sub 2} and glycerol-3-phosphate, 15 mM KHCO{sub 3}, and 0.1M Bis-tris-propane, pH 8.0 incubated at 35C. At the standard incubation temperature of 25C, fattyacid synthesis was linear from up to 6 hours with 80 to 100 {mu}g/mL plastid protein. ATP and CoA were absolute requirements, whereas KHCO{sub 3}, divalent cations and reduced nucleotides all improved activity by 80 to 85%. Mg{sup 2+} and NADH were the preferred cation and nucleotide, respectively. Dithiothreitol and detergents were generally inhibitory. The radioactive products of fattyacid biosynthesis were approximately 33% 16:0, 10% 18:0 and 56% 18:1 and generally did not vary with increasing concentrations of each cofactor.

Perfluorooctanoic acid (PFOA) is a degradation-resistant compound with a carbon-fluorine bond. Although PFOA emissions have been reduced since 2000, it remains persistent in the environment. Several studies on laboratory animals indicate that PFOA exposure can impact male fertility. Here, adult male mice received either PFOA (1.25, 5 or 20 mg/kg/d) or an equal volume of water for 28 d consecutively. PFOA accumulated in the epididymis in a dose-dependent manner and resulted in reduced epididymis weight, lower levels of triglycerides (TG), cholesterol (CHO), and free fattyacids (FFA), and activated AKT/AMPK signaling in the epididymis. Altered polyunsaturated fattyacid (PUFA) compositions, such as a higher arachidonic acid:linoleic acid (AA:LA) ratio, concomitant with excessive oxidative stress, as demonstrated by increased malonaldehyde (MDA) and decreased glutathione peroxidase (GSH-Px) in the epididymis, were observed in epididymis tissue following treatment with PFOA. These results indicate that the epididymis is a potential target of PFOA. Oxidative stress and PUFA alteration might help explain the sperm injury and male reproductive dysfunction induced by PFOA exposure. PMID:27262104

Peroxisome proliferator-activated receptor α (PPARα) is a key regulator of lipid homeostasis in hepatocytes and target for fattyacids and hypolipidemic drugs. How these signaling molecules reach the nuclear receptor is not known; however, similarities in ligand specificity suggest the liver fattyacid binding protein (L-FABP) as a possible candidate. In localization studies using laser-scanning microscopy, we show that L-FABP and PPARα colocalize in the nucleus of mouse primary hepatocytes. Furthermore, we demonstrate by pull-down assay and immunocoprecipitation that L-FABP interacts directly with PPARα. In a cell biological approach with the aid of a mammalian two-hybrid system, we provide evidence that L-FABP interacts with PPARα and PPARγ but not with PPARβ and retinoid X receptor-α by protein–protein contacts. In addition, we demonstrate that the observed interaction of both proteins is independent of ligand binding. Final and quantitative proof for L-FABP mediation was obtained in transactivation assays upon incubation of transiently and stably transfected HepG2 cells with saturated, monounsaturated, and polyunsaturated fattyacids as well as with hypolipidemic drugs. With all ligands applied, we observed strict correlation of PPARα and PPARγ transactivation with intracellular concentrations of L-FABP. This correlation constitutes a nucleus-directed signaling by fattyacids and hypolipidemic drugs where L-FABP acts as a cytosolic gateway for these PPARα and PPARγ agonists. Thus, L-FABP and the respective PPARs could serve as targets for nutrients and drugs to affect expression of PPAR-sensitive genes. PMID:11226238

The role of membrane fattyacid composition in the resistance of Pseudomonas aeruginosa ATCC 15442 to the bactericidal activity of Quaternary Ammonium Compounds (QACs) was investigated. The strain was grown in a medium with increasing concentrations of a QAC, benzyldimethyltetradecylammonium chloride (C14) and two non-QACs, sodium dichloroisocyanurate and tri-sodium phosphate. In the presence of C14 only, the strain was able to grow in concentrations higher than the minimal inhibitory concentration. As the strain adapted to C14, resistance to bactericidal activity of the same biocide increased. For the non-QACs, no change was noted when cells were grown in the presence of biocides. The C14-adapted cells showed variations in membrane fattyacid composition. A hierarchical clustering analysis was used to compare all fattyacid compositions of cultures in the presence, or not, of the three biocides used here and another QAC studied previously. The clusters obtained underlined specific variations of membrane fattyacids in response to the presence of QACs. Furthermore, with a simple linear regression analysis, a relationship was shown between the membrane fattyacids and the resistance developed by the strain against the bactericidal activity of C14. PMID:10594715

Although movement of fattyacids between bilayers can occur spontaneously, it has been postulated that intracellular movement is facilitated by a class of proteins named fattyacid binding proteins (FABP). In this study we have incorporated long chain fattyacids into multilamellar liposomes made of phosphatidylcholine, incubated them with rat liver microsomes containing an active acyl-CoA synthetase, and measured formation of acyl-CoA in the absence or presence of FABP purified from rat liver. FABP increased about 2-fold the accumulation of acyl-CoA when liposomes were the fattyacid donor. Using fattyacid incorporated into liposomes made either of egg yolk lecithin or of dipalmitoylphosphatidylcholine, it was found that the temperature dependence of acyl-CoA accumulation in the presence of FABP correlated with both the physical state of phospholipid molecules in the liposomes and the binding of fattyacid to FABP, suggesting that fattyacid must first desorb from the liposomes before FABP can have an effect. An FABP-fattyacid complex incubated with microsomes, in the absence of liposomes, resulted in greater acyl-CoA formation than when liposomes were present, suggesting that desorption of fattyacid from the membrane is rate-limiting in the accumulation of acyl-CoA by this system. Finally, an equilibrium dialysis cell separating liposomes from microsomes on opposite sides of a Nuclepore filter was used to show that liver FABP was required for the movement and activation of fattyacid between the compartments. These studies show that liver FABP interacts with fattyacid that desorbs from phospholipid bilayers, and promotes movement to a membrane-bound enzyme, suggesting that FABP may act intracellularly by increasing net desorption of fattyacid from cell membranes. PMID:3446187

c-AMP dependent protein kinase (protein kinase A, PKA) is an important enzyme involved in the regulation of an increasing number of physiological processes including immune function, cardiovascular disease, memory disorders and cancer. The objective of this study was to evaluate the PKA inhibitory activity of a range of algal extracts, along with their fattyacid composition. Six algal species were investigated including two Chlorophyta (Codium dimorphum and Ulva lactuca), two Phaeophyta (Phyllospora comosa and Sargassum sp.) and two Rhodophyta (Prionitis linearis and Corallina vancouveriensis), with the order of PKA inhibitory activity of their extracts identified as follows: brown seaweeds > red seaweeds > green seaweeds with the brown alga Sargassum sp. exhibiting the highest PKA inhibitory activity (84% at 100 microg/mL). GC/MS analysis identified a total of 18 fattyacids in the six algal extracts accounting for 72-87% of each extract, with hexadecanoic acid and 9,12-octadecadienoic acid as the dominant components. The most active extract (Sargassum sp.) also contained the highest percentage of the saturated C14:0 fattyacid (12.8% of the total extract), which is a known to inhibit PKA. These results provide the first description of the PKA inhibitory activity of marine algae along with the first description of the fattyacid composition of these six algal species from South Eastern Australian waters. Importantly, this study reveals that abundant and readily available marine algae are a new and relatively unexplored source of PKA inhibitory compounds. PMID:22908583

This study examined whether blood fattyacid levels, vitamin D status, and/or physical activity are associated with physical fitness scores; a measure of mood, Patient Health Questionnaire-9; and a measure of resiliency, Dispositional Resiliency Scale-15 in active duty Soldiers. 100 active duty males at Fort Hood, Texas, underwent a battery of psychometric tests, anthropometric measurements, and fitness tests, and they also provided fasting blood samples for fattyacid and vitamin D analysis. Pearson bivariate correlation analysis revealed significant correlations among psychometric tests, anthropometric measurements, physical performance, reported physical inactivity (sitting time), and fattyacid and vitamin D blood levels. On the basis of these findings, a regression equation was developed to predict a depressed mood status as determined by the Patient Health Questionnaire-9. The equation accurately predicted depressed mood status in 80% of our participants with a sensitivity of 76.9% and a specificity of 80.5%. Results indicate that the use of a regression equation may be helpful in identifying Soldiers at higher risk for mental health issues. Future studies should evaluate the impact of exercise and diet as a means of improving resiliency and reducing depressed mood in Soldiers. PMID:27612362

Supplementation of long-chain polyunsaturated fattyacids (LCPUFAs) is advocated during pregnancy in some countries although very little information is available on their effects on placental ability to take up these fattyacids for fetal supply to which the fetal growth and development are critically dependent. To identify the roles of LCPUFAs on placental fattyacid transport function, we examined the effects of LCPUFAs on the uptake of fattyacids and expression of fattyacid transport/metabolic genes using placental trophoblast cells (BeWo). Following 24 h incubation of these cells with 100 microM of LCPUFAs (arachidonic acid, 20:4n-6, eicosapentaenoic acid, 20:5n-3, or docosahexaenoic acid, 22:6n-3), the cellular uptake of [(14)C] fattyacids was increased by 20-50%, and accumulated fattyacids were preferentially incorporated into phospholipid fractions. Oleic acid (OA, 18:1n-9), on the other hand, could not stimulate fattyacid uptake. LCPUFAs and OA increased the gene expression of ADRP whilst decreased the expression of ASCL3, ACSL4, ACSL6, LPIN1, and FABP3 in these cells. However, LCPUFAs but not OA increased expression of ACSL1 and ACSL5. Since acyl-CoA synthetases are involved in cellular uptake of fattyacids via activation for their channelling to lipid metabolism and/or for storage, the increased expression of ACSL1 and ACLS5 by LCPUFAs may be responsible for the increased fattyacid uptake. These findings demonstrate that LCPUFA may function as an important regulator of general fattyacid uptake in trophoblast cells and may thus have impact on fetal growth and development. PMID:19880178

The level of unsaturation of the constituent fattyacids of many glycerolipids in plant membranes is modified by environmental factors. The measurement of the rate of the desaturation of these fattyacids is essential to an understanding of how plants adapt to changing environments. This is difficult because of the complexity of the system and the problems involved in measuring rates of these enzyme reactions in cell-free preparations. A computer program has been developed that simulates the synthesis of galactosyldiacylglycerols and desaturation of their fattyacids in chloroplasts. The program uses the rate of incorporation and distribution of 14C in fattyacids after 14CO2 feeding to estimate rates of desaturation in the fattyacids of glycerolipids. Data are presented to demonstrate the use of the program in comparing rates of desaturation in the five enzyme reactions associated with monogalactosyldiacylglycerol in the chloroplastic pathway of leaves from Brassica napus. The method represents a quick, reliable, and accurate measure of desaturase activity in vivo and is the only method available to estimate desaturase activity of all five enzymes at the same time. PMID:12231750

The activities of lipogenic enzymes appear to fluctuate with changes in the level and type of dietary fats. Polyunsaturated fattyacids (PUFAs) are known to induce on hepatic de novo lipogenesis (DNL) the highest inhibitory effect, which occurs through a long-term adaptation. Data on the acute effects of dietary fattyacids on DNL are lacking. In this study with rats, the acute 1-day effect of high-fat (15 % w/w) diets (HFDs) enriched in saturated fattyacids (SFAs) or unsaturated fattyacids (UFAs), i.e., monounsaturated (MUFA) and PUFA, of the ω-6 and ω-3 series on DNL and plasma lipid level was investigated; a comparison with a longer time feeding (21 days) was routinely carried out. After 1-day HFD administration UFA, when compared to SFA, reduced plasma triacylglycerol (TAG) level and the activities of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fattyacid synthase (FAS), a decreased activity of the citrate carrier (CIC), a mitochondrial protein linked to lipogenesis, was also detected. In this respect, ω-3 PUFA was the most effective. On the other hand, PUFA maintained the effects at longer times, and the acute inhibition induced by MUFA feeding on DNL enzyme and CIC activities was almost nullified at 21 days. Mitochondrial fattyacid composition was slightly but significantly changed both at short- and long-term treatment, whereas the early changes in mitochondrial phospholipid composition vanished in long-term experiments. Our results suggest that in the early phase of administration, UFA coordinately reduced both the activities of de novo lipogenic enzymes and of CIC. ω-3 PUFA showed the greatest effect. PMID:27312217

All positive strand (+RNA) viruses of eukaryotes replicate their genomes in association with membranes. The mechanisms of membrane remodeling in infected cells represent attractive targets for designing future therapeutics, but our understanding of this process is very limited. Elements of autophagy and/or the secretory pathway were proposed to be hijacked for building of picornavirus replication organelles. However, even closely related viruses differ significantly in their requirements for components of these pathways. We demonstrate here that infection with diverse picornaviruses rapidly activates import of long chain fattyacids. While in non-infected cells the imported fattyacids are channeled to lipid droplets, in infected cells the synthesis of neutral lipids is shut down and the fattyacids are utilized in highly up-regulated phosphatidylcholine synthesis. Thus the replication organelles are likely built from de novo synthesized membrane material, rather than from the remodeled pre-existing membranes. We show that activation of fattyacid import is linked to the up-regulation of cellular long chain acyl-CoA synthetase activity and identify the long chain acyl-CoA syntheatse3 (Acsl3) as a novel host factor required for polio replication. Poliovirus protein 2A is required to trigger the activation of import of fattyacids independent of its protease activity. Shift in fattyacid import preferences by infected cells results in synthesis of phosphatidylcholines different from those in uninfected cells, arguing that the viral replication organelles possess unique properties compared to the pre-existing membranes. Our data show how poliovirus can change the overall cellular membrane homeostasis by targeting one critical process. They explain earlier observations of increased phospholipid synthesis in infected cells and suggest a simple model of the structural development of the membranous scaffold of replication complexes of picorna-like viruses, that may be

The first total synthesis for the (Z)-16-methyl-11-heptadecenoic acid, a novel fattyacid from the sponge Dragmaxia undata, was accomplished in seven steps and in a 44% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 10-bromo-1-decanol followed by a second acetylide coupling to the short-chain 1-bromo-4-methylpentane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fattyacid and the cis double bond stereochemistry of the natural acid was established. The title compound displayed antiprotozoal activity against Leishmania donovani (IC50 = 165.5 ± 23.4 µM) and inhibited the leishmania DNA topoisomerase IB enzyme (LdTopIB) with an IC50 = 62.3 ± 0.7 µM. PMID:21129369

Cardiac hypertrophy is characterised by an imbalance between lipid uptake and fattyacid β-oxidation leading to an accumulation of lipids, particularly triacylglycerol (TAG). It is unclear whether uptake mechanisms such as lipoprotein lipase (LPL) can be attenuated to diminish this uptake. Rats were cold acclimated to induce cardiac hypertrophy and increase cardiac LPL. Lipid uptake and metabolism were altered by feeding a ‘Western-style’ high fat diet (WSD) or feeding oxfenicine (2 g/L) in the drinking water. Diastolic stiffness (increased volume change/unit pressure change) was induced in hypertrophied hearts for rats fed WSD (P

Phospholipid (PL), glycolipid (GL), and neutral lipid (NL) FA, and the lipopolysaccharide 2- and 3-hydroxy (LPS 2-OH and 3-OH) FA of activated sludges and extracted extracellular polymeric substances (EPS) were determined on samples collected from two wastewater treatment plants. EPS extracted from sludges by means of sonication and cation exchange contained proteins (43.4%), humic-like substances (11.5%), nucleic acids (10.9%), carbohydrates (9.9%), and lipid-bound FA (1.8%). The lipids associated with EPS were composed of GL, PL, NL, and LPS acids in proportions of 61, 21, 16, and 2%, respectively. The profiles of lipid-bound FA in activated sludges and EPS were similar (around 85 separate FA were identified). The FA signatures observed can be attributed to the likely presence of yeasts, fungi, sulfate-reducing bacteria, gram-positive and gram-negative bacteria, and, in lesser quantities, mycobacteria. Comparison of data from the dates of sampling (January and September) showed that there were more unsaturated PLFA in the EPS extracted from the activated sludges sampled in January. This observation could be partly related to microorganism adaptation to temperature variations. The comparison between two wastewater treatment plants showed that the FA profiles were similar, although differences in microbial community structure were also seen. Most of the FA in sludges had an even number of carbons. PMID:14669975

Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI), and ACAD9 mutations are recognized as a frequent cause of CI deficiency. ACAD9 also retains enzyme ACAD activity for long-chain fattyacids in vitro, but the biological relevance of this function remains controversial partly because of the tissue specificity of ACAD9 expression: high in liver and neurons and minimal in skin fibroblasts. In this study, we hypothesized that this enzymatic ACAD activity is required for full fattyacid oxidation capacity in cells expressing high levels of ACAD9 and that loss of this function is important in determining phenotype in ACAD9-deficient patients. First, we confirmed that HEK293 cells express ACAD9 abundantly. Then, we showed that ACAD9 knockout in HEK293 cells affected long-chain fattyacid oxidation along with Cl, both of which were rescued by wild type ACAD9. Further, we evaluated whether the loss of ACAD9 enzymatic fattyacid oxidation affects clinical severity in patients with ACAD9 mutations. The effects on ACAD activity of 16 ACAD9 mutations identified in 24 patients were evaluated using a prokaryotic expression system. We showed that there was a significant inverse correlation between residual enzyme ACAD activity and phenotypic severity of ACAD9-deficient patients. These results provide evidence that in cells where it is strongly expressed, ACAD9 plays a physiological role in fattyacid oxidation, which contributes to the severity of the phenotype in ACAD9-deficient patients. Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fattyacid oxidation dysfunctions. PMID:25721401

A series of fattyacid conjugates of trans-3,4-dihydroxy-1-selenolane (DHS) were synthesized by reacting DHS with appropriate acid chlorides. The obtained monoesters were evaluated for their antioxidant capacities by the lipid peroxidation assay using a lecithin/cholesterol liposome as a model system. The observed antioxidant capacities against accumulation of the lipid hydroperoxide (LOOH) increased with increasing the alkyl chain length and became saturated for dodecanoic acid (C12) or higher fattyacid monoesters, for which the capacities were much greater than those of DHS, its tridecanoic acid (C13) diester, and PhSeSePh. On the other hand, the bacteriostatic activity of myristic acid (C14) monoester, evaluated through the colony formation assay using Bacillus subtilis, indicated that it has higher affinity to bacterial cell membranes than parent DHS. Since DHS-fattyacid conjugates would inhibit lipid peroxidation through glutathione peroxidase (GPx)-like 2e- mechanism, higher fattyacid monoesters of DHS can mimic the function of GPx4, which interacts with LOOH to reduce it to harmless alcohol (LOH). Importance of the balance between hydrophilicity and lipophilicity for the design of effective GPx4 mimics was suggested. PMID:26198222

Previously it has been shown by our group that berberine and palmatine, penetrating cations of plant origin, when conjugated with plastoquinone (SkQBerb and SkQPalm), can accumulate in isolated mitochondria or in mitochondria of living cells and effectively protect them from oxidative damage. In the present work, we demonstrate that SkQBerb, SkQPalm, and their analogs lacking the plastoquinone moiety (C10Berb and C10Palm) operate as mitochondria-targeted compounds facilitating protonophorous effect of free fattyacids. These compounds induce proton transport mediated by small concentrations of added fattyacids both in planar and liposomal model lipid membranes. In mitochondria, such an effect can be carried out by endogenous fattyacids and the adenine nucleotide translocase. PMID:23026390

Neutrophils are well-known to act in the destruction of invading microorganisms. They have also been implicated in the activation of other immune cells including B- and T-lymphocytes and in the resolution of inflammation and tissue regeneration. Neutrophils are produced in the bone marrow and released into the circulation from where they migrate to tissues to perform their effector functions. Neutrophils are in constant contact with fattyacids that can modulate their function, activation and fate (survival or cell death) through different mechanisms. In this review, the effects of fattyacids pertaining to five classes, namely, long-chain saturated fattyacids (LCSFAs), short-chain fattyacids (SCFAs), and omega-3 (n-3), omega-6 (n-6) and omega-9 (n-9) unsaturated fattyacids, on neutrophils and the relevance of these effects for disease development are discussed. PMID:25987417

Plasma fattyacid (FA) composition is known to be an indicator of dietary fat quality, but the associations of other dietary factors with plasma FA composition remain unknown in children. We investigated the cross-sectional associations of food consumption with the proportions of FA and estimated desaturase activities in plasma cholesteryl esters (CE) and phospholipids (PL) among children. The subjects were a population sample of 423 children aged 6–8 years examined at baseline of The Physical Activity and Nutrition in Children (PANIC) Study. We assessed food consumption by food records and plasma FA composition by gas chromatography. We used linear regression models adjusted for age, sex, physical activity and total energy intake to analyze the associations. A higher consumption of vegetable oil-based margarine (fat 60–80 %) was associated with a higher proportion of linoleic and α-linolenic acids in plasma CE and PL. A higher consumption of high-fiber grain products was related to a lower proportion of oleic acid in CE and PL. The consumption of candy was directly associated with the proportion of palmitoleic and oleic acid in plasma CE. The consumption of vegetable oil-based margarine was inversely associated with estimated stearoyl-CoA-desaturase activity in plasma CE and PL and the consumption of candy was directly related to it in plasma CE. The results of our study suggest that plasma FA composition is not only a biomarker for dietary fat quality but also reflects the consumption of high-fiber grain products and foods high in sugar among children. PMID:24659110

Because alterations in blood fattyacid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2

Background & Aims Nonalcoholic fatty liver disease (NAFLD) is a common consequence of human and rodent obesity. Disruptions in lipid metabolism lead to accumulation of triglycerides and fattyacids, which can promote inflammation and fibrosis and lead to nonalcoholic steatohepatitis (NASH). Circulating levels of fibroblast growth factor (FGF)21 increase in patients with NAFLD or NASH, so we assessed the role of FGF21 in the progression of murine fatty liver disease, independent of obesity, caused by methionine and choline deficiency. Methods C57BL/6 wild-type and FGF21-knockout (FGF21-KO) mice were placed on methionine- and choline-deficient (MCD), high-fat, or control diets for 8–16 weeks. Mice were weighed; serum and liver tissues were collected and analyzed for histology, levels of malondialdehyde and liver enzymes, gene expression, and lipid content. Results The MCD diet increased hepatic levels of FGF21 mRNA more than 50-fold and serum levels 16-fold, compared with the control diet. FGF21-KO mice had more severe steatosis, fibrosis, inflammation, and peroxidative damage than wild-type C57BL/6 mice. FGF21-KO mice had reduced hepatic fattyacidactivation and β oxidation, resulting in increased levels of free fattyacid. FGF21-KO mice given continuous subcutaneous infusions of FGF21 for 4 weeks while on MCD diets had reduced steatosis and peroxidative damage, compared with mice not receiving FGF21. The expression of genes that regulate inflammation and fibrosis were reduced in FGF21-KO mice given FGF21, similar to those of wild-type mice. Conclusions FGF21 regulates fattyacidactivation and oxidation in livers of mice. In the absence of FGF21, accumulation of inactivated fattyacids results in lipotoxic damage and increased steatosis. PMID:25083607

The peroxisome proliferator-activated receptor gamma (PPARγ) gene plays an important role in the biosynthesis process controlled by a number of fattyacid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the PPARγ gene and the fattyacid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fattyacid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fattyacids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the PPARγ gene affected fattyacid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle. PMID:26732443

Western life style, and high calorie diet in particular is causing major health problems such as insulin resistance, hepatic steatosis and heart disease in the modern age. High fat diet (HFD) induces similar changes in mice, such as increased body weight, hypercholesterolemia and accumulation of triglycerides in the liver. These changes can be ameliorated by the administration of some Lactobacillus species. The focus of this study was to analyze the fattyacid content of liver, heart and brain tissues of mice fed HFD and administered with either Lactobacillus plantarum WCFS1 or Lactobacillus rhamnosus LA68, and to analyze the fattyacid content of these organs after a two months washout period. The fattyacid composition of mouse liver tissue changed significantly due to probiotic administration during a 12 weeks HFD regime and active Lactobacillus administration had a slightly reversing effect toward the standard mouse diet group, but after the washout period these changes disappeared. The fattyacid composition of the heart and brain tissues was significantly changed in the HFD regime but probiotic administration had no significant influence on the fattyacid profile of these two organs. Upon the 8 weeks washout period the only remaining beneficial effect was the significantly lower mouse weight in the supplemented groups compared to the HFD group. PMID:27231730

The peroxisome proliferator-activated receptor gamma (PPARγ) gene plays an important role in the biosynthesis process controlled by a number of fattyacid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the PPARγ gene and the fattyacid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fattyacid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fattyacids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the PPARγ gene affected fattyacid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle. PMID:26732443

A comparative analysis of fattyacids (FA) in neutral and phospholipids of digestive gland and pedal muscle has been performed in molluscs from various ecological groups differing by belonging to sea or fresh water, trophic types or the associated motor activity. In freshwater pulmonary gastropods Lymnaea stagnalis and Limnaea ovalis and marine prosobranchial molluscs Buccinum undatum and Littorina littorea the total content of omega3-acids in phospholipids of the studied tissues differed more than twice, predominantly due to the combined effect of temperature and salinity of the habitat. The lower viscosity of cell membranes in marine species (omega3/omega6 < 1) is determined to the greatest degree by the presence of eicosapentaenoic acid that accounts for 22-25 % of the FA sum in marine species. Comparison of the molluscs by their trophic belonging has revealed the presence of linoleic acid in triglycerides in digestive glands of phytophages (8-12 %), but the practically complete absence of this acid in the predator B. undulatum (<0.8 %. By mobility, L. littorea inhabiting the high-low tide littoral was inferior to freshwater pulmonary gastropods and to marine predator, as it stops moving twice a day during the low tide. In phospholipids of pedal muscle of this mollusc the amount of long-chain polyunsaturated C:22 FA was 3-6 times lower than that in other studied species, which might possibly indicate the role of these acids in functioning of the pedal muscle contractile tissue. On the whole, use of the FA characteristics as parameters determining belonging to certain ecological group requires a certain caution due to a complex action of biotic and abiotic factors on the animal metabolism. The exception is the omega3/omega6 ratio in total phospholipids of freshwater and marine gastropods. PMID:19370988

The total fatty constituents of slash pine (Pinus elliottii) tissue cultures, seeds, and seedlings were examined by GLC and MS. Qualitatively, the fattyacid composition of these tissues was found to be very similar to that reported for other pine species. The fattyacid contents of the tissue cultures resembled that of the seedling tissues. The branched-chain C(sub 17) acid reported for several other Pinus species was confirmed as the anteiso isomer.

The fattyacid profile of kenaf (Hibiscus cannabinus L.) seed oil has been the subject of several previous reports in the literature. These reports vary considerably regarding the presence and amounts of specific fattyacids, notably epoxyoleic acid but also cyclic (cyclopropene and cyclopropane) fa...

Steady state concentrations of ATP and ADP in vivo are similar at low and high cardiac workloads; however, the mechanisms that regulate the activation of substrate metabolism and oxidative phosphorylation that supports this stability are poorly understood. We tested the hypotheses that (1) there is parallel activation of mitochondrial and cytosolic dehydrogenases in the transition from low to high workload, which increases NADH/NAD+ ratio in both compartments, and (2) this response does not require an increase in fattyacid oxidation (FAO). Anaesthetized pigs were subjected to either sham treatment, or an abrupt increase in cardiac workload for 5 min with dobutamine infusion and aortic constriction. Myocardial oxygen consumption and FAO were increased 3- and 2-fold, respectively, but ATP and ADP concentrations did not change. NADH-generating pathways were rapidly activated in both the cytosol and mitochondria, as seen in a 40% depletion in glycogen stores, a 3.6-fold activation of pyruvate dehydrogenase, and a 50% increase in tissue NADH/NAD+. Simulations from a multicompartmental computational model of cardiac energy metabolism predicted that parallel activation of glycolysis and mitochondrial metabolism results in an increase in the NADH/NAD+ ratio in both cytosol and mitochondria. FAO was blocked by 75% in a third group of pigs, and a similar increase in and the NAHD/NAD+ ratio was observed. In conclusion, in the transition to a high cardiac workload there is rapid parallel activation of substrate oxidation that results in an increase in the NADH/NAD+ ratio. PMID:17185335

Thyroid hormones play an important role in the control of metabolism of vertebrates. This investigation was carried out to examine the effects of triiodothyronine (T3) and polyunsaturated fattyacids (PUFA) on lipid peroxidation in rat liver. Male Wistar strain of rats treated with 6-propylthiouracil (6-PTU) showed no significant change in lipid peroxidation as evident from the generation of malondialdehyde and conjugated dienes. However, in PUFA fed animals as well as 6-PTU + PUFA + T3 treated groups, increased peroxidation products were found. Superoxide dismutase (SOD) activity was low in 6-PTU, 6-PTU + PUFA, PUFA, 6-PTU + PUFA + T3 treated animals while glutathione peroxidase (GPx) activity was high in these groups. Catalase activity was low in all treated groups except PUFA alone fed animals. Glutathione reductase (GR) activity was decreased by 6-PTU treatment and increased in PTU + PUFA fed rats. Cellular glutathione level was high in PUFA and low in PTU-treated groups. From these results it can be concluded that both T3 and PUFA have profound influence on lipid peroxidation and antioxidant enzyme activities in rat liver. PMID:11794465

Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate that cis-2-decenoic acid (cis-DA), a fattyacid signaling molecule, is able to change the status of Pseudomonas aeruginosa and Escherichia coli persister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, including acpP, 16S rRNA, atpH, and ppx. Given that most antimicrobials target actively growing cells, we also explored the effect of cis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials and cis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence of cis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fattyacid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state. PMID:25192989

Short-chain fattyacids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fattyacid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fattyacid production, such as deletion of the fadD and fadE that initiates the fattyacid degradation cycle and overexpression of fadR that is a global transcriptional activator of fattyacid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fattyacid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fattyacid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product. PMID:27466817

Short-chain fattyacids (SCFAs), such as butyric acid, have a broad range of applications in chemical and fuel industries. Worldwide demand of sustainable fuels and chemicals has encouraged researchers for microbial synthesis of SCFAs. In this study we compared three thioesterases, i.e., TesAT from Anaerococcus tetradius, TesBF from Bryantella formatexigens and TesBT from Bacteroides thetaiotaomicron, for production of SCFAs in Escherichia coli utilizing native fattyacid synthesis (FASII) pathway and modulated the genetic and bioprocess parameters to improve its yield and productivity. E. coli strain expressing tesBT gene yielded maximum butyric acid titer at 1.46 g L-1, followed by tesBF at 0.85 g L-1 and tesAT at 0.12 g L-1. The titer of butyric acid varied significantly depending upon the plasmid copy number and strain genotype. The modulation of genetic factors that are known to influence long chain fattyacid production, such as deletion of the fadD and fadE that initiates the fattyacid degradation cycle and overexpression of fadR that is a global transcriptional activator of fattyacid biosynthesis and repressor of degradation cycle, did not improve the butyric acid titer significantly. Use of chemical inhibitor cerulenin, which restricts the fattyacid elongation cycle, increased the butyric acid titer by 1.7-fold in case of TesBF, while it had adverse impact in case of TesBT. In vitro enzyme assay indicated that cerulenin also inhibited short chain specific thioesterase, though inhibitory concentration varied according to the type of thioesterase used. Further process optimization followed by fed-batch cultivation under phosphorous limited condition led to production of 14.3 g L-1 butyric acid and 17.5 g L-1 total free fattyacid at 28% of theoretical yield. This study expands our understanding of SCFAs production in E. coli through FASII pathway and highlights role of genetic and process optimization to enhance the desired product. PMID:27466817

Peroxisome proliferator-activated receptor γ (PPARγ) belongs to the family of nuclear nuclear receptors and is mainly expressed in adipose tissue, hematopoietic cells and the large intestine. Contrary to other nuclear receptors that mainly bind a single specific ligand, there are numerous natural PPARγ ligands, in particular fattyacids or their derivatives called eicosanoids. PPARγ have pleiotropic functions: (i) glucose and lipid metabolism regulation, (ii) anti-inflammatory properties, (iii) oxidative stress inhibition, (iv) improvement of endothelial function. Its role has been mainly studied by the use synthetic agonists. In this review, we will focus on the effects of PPARγ mediated through fattyacids and how these have beneficial health properties. PMID:26632493

Non-alcoholic fatty liver disease (NAFLD) is currently evolving as the most common liver disease worldwide. It may progress to liver cirrhosis and liver cancer and is poised to represent the most common indication for liver transplantation in the near future. The pathogenesis of NAFLD is multifactorial and not fully understood, but it represents an insulin resistance state characterized by a cluster of cardiovascular risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension. Importantly, NAFLD also has evolved as independent risk factor for cardiovascular disease. Unfortunately thus far no established treatment does exist for NAFLD. The bile acid-activated nuclear farnesoid X receptor (FXR) has been shown to play a role not only in bile acid but also in lipid and glucose homeostasis. Specific targeting of FXR may be an elegant and very effective way to readjust dysregulated nuclear receptor-mediated metabolic pathways. This review discusses the body's complex response to the activation of FXR with its beneficial actions but also potential undesirable side effects. PMID:22187656

Adipose tissue fattyacid storage varies according to sex, adipose tissue depot, and degree of fat gain. However, the mechanism(s) for these variations is not completely understood. We examined whether differences in adipose tissue glycerol-3-phosphate acyltransferase (GPAT) might play a role in these variations. We optimized an enzyme activity assay for total GPAT and GPAT1 activity in human adipose tissue and measured GPAT activity. Omental and subcutaneous adipose tissue was collected from obese and nonobese adults for measures of GPAT and GPAT1 activities, ex vivo palmitate storage, acyl-CoA synthetase (ACS) and diacylglycerol-acyltransferase (DGAT) activities, and CD36 protein. Total GPAT and GPAT1 activities decreased as a function of adipocyte size in both omental (r = −0.71, P = 0.003) and subcutaneous (r = −0.58, P = 0.04) fat. The relative contribution of GPAT1 to total GPAT activity increased as a function of adipocyte size, accounting for up to 60% of GPAT activity in those with the largest adipocytes. We found strong, positive correlations between ACS, GPAT, and DGAT activities for both sexes and depots (r values 0.58–0.91) and between these storage factors and palmitate storage rates into TAG (r values 0.55–0.90). We conclude that: 1) total GPAT activity decreases as a function of adipocyte size; 2) GPAT1 can account for over half of adipose GPAT activity in hypertrophic obesity; and 3) ACS, GPAT, and DGAT are coordinately regulated. PMID:25738782

The agar diffusion assay was used to examine antibacterial activity of alkaline salts of fattyacids (FA). Wells in agar media seeded with bacteria were filled with FA-potassium hydroxide (KOH) solutions, plates were incubated, and zones of inhibition were measured. The relationship between bacteric...

Saccharomyces cerevisiae shows great potential for development of bioreactor systems geared towards the production of high-value lipids such as polyunsaturated omega-3 fattyacids, the yields of which are largely dependent on the activity of ectopically-expressed enzymes. Here we show that the addit...

The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fattyacid. The title compound displayed antiprotozoal activity against Leishmania donovani (EC50 = 19.8 μg/ml) and inhibited the leishmania DNA topoisomerase IB at concentrations of 50 μM. PMID:19527698

Highlights: •TC, a CB2R specific agonist, stimulates SIRT1 activity by PKA/CREB pathway. •TC promotes PGC-1α transcriptional activity by increasing its deacetylation. •TC increases the expression of genes linked to FAO and promotes the rate of FAO. •The effects of TC in FAO are dependent on CB2R. •Suggesting CB2R as a target to treat diseases with lipid dysregulation. -- Abstract: Abnormal fattyacid oxidation has been associated with obesity and type 2 diabetes. At the transcriptional level, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) has been reported to strongly increase the ability of hormone nuclear receptors PPARα and ERRα to drive transcription of fattyacid oxidation enzymes. In this study, we report that a specific agonist of the type 2 cannabinoid receptor (CB2R) can lead to fattyacid oxidation through the PGC-1α pathway. We have found that CB2R is expressed in differentiated C2C12 myotubes, and that use of the specific agonist trans-caryophyllene (TC) stimulates sirtuin 1 (SIRT1) deacetylase activity by increasing the phosphorylation of cAMP response element-binding protein (CREB), thus leading to increased levels of PGC-1α deacetylation. This use of TC treatment increases the expression of genes linked to the fattyacid oxidation pathway in a SIRT1/PGC-1α-dependent mechanism and also drastically accelerates the rate of complete fattyacid oxidation in C2C12 myotubes, neither of which occur when CB2R mRNA is knocked down using siRNA. These results reveal that activation of CB2R by a selective agonist promotes lipid oxidation through a signaling/transcriptional pathway. Our findings imply that pharmacological manipulation of CB2R may provide therapeutic possibilities to treat metabolic diseases associated with lipid dysregulation.

Uptake and metabolism of saturated (16:0, 18:0) and unsaturated (18:1(n-9), 18:2(n-6), 18:3(n-3)) fattyacids by cultured epimastigotes of Trypanosoma cruzi were studied. Between 17.5 and 33.5% of the total radioactivity of (1-/sup 14/C)labeled fattyacids initially added to the culture medium was incorporated into the lipids of T. cruzi and mostly choline and ethanolamine phospholipids. As demonstrated by argentation thin layer chromatography, gas liquid chromatography and ozonolysis of the fattyacids synthesized, exogenous palmitic acid was elongated to stearic acid, and the latter was desaturated to oleic acid and 18:2 fattyacid. The 18:2 fattyacid was tentatively identified as linoleic acid with the first bond in the delta 9 position and the second bond toward the terminal methyl end. Exogenous stearic acid was also desaturated to oleic and 18:2 fattyacid, while oleic acid was only converted into 18:2. All of the saturated and unsaturated fattyacids investigated were also converted to a small extent (2-4%) into polyunsaturated fattyacids. No radioactive aldehyde methyl ester fragments of less than nine carbon atoms were detected after ozonolysis of any of the fattyacids studied. These results demonstrate the existence of delta 9 and either delta 12 or delta 15 desaturases, or both, in T. cruzi and suggest that delta 6 desaturase or other desaturases of the animal type are likely absent in cultured forms of this organism.

The consumption of trans fattyacid (TFA) is linked to the elevation of LDL cholesterol and is considered to be a major health risk factor for coronary heart disease. Despite several decades of extensive research on this subject, the underlying mechanism of how TFA modulates serum cholesterol levels remains elusive. In this study, we examined the molecular interaction of TFA-derived phospholipid with cholesterol and the membrane receptor rhodopsin in model membranes. Rhodopsin is a prototypical member of the G-protein coupled receptor family. It has a well-characterized structure and function and serves as a model membrane receptor in this study. Phospholipid–cholesterol affinity was quantified by measuring cholesterol partition coefficients. Phospholipid–receptor interactions were probed by measuring the level of rhodopsin activation. Our study shows that phospholipid derived from TFA had a higher membrane cholesterol affinity than their cis analogues. TFA phospholipid membranes also exhibited a higher acyl chain packing order, which was indicated by the lower acyl chain packing free volume as determined by DPH fluorescence and the higher transition temperature for rhodopsin thermal denaturation. The level of rhodopsin activation was diminished in TFA phospholipids. Since membrane cholesterol level and membrane receptors are involved in the regulation of cholesterol homeostasis, the combination of higher cholesterol content and reduced receptor activation associated with the presence of TFA–phospholipid could be factors contributing to the elevation of LDL cholesterol. PMID:15766276

The long-chain omega-3 polyunsaturated fattyacids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

Fattyacids are basic renewable chemical building blocks that can be used as intermediates for a multitude of products. Today the global value of fattyacids exceeds 18 billion dollars and is expected to increase to nearly 26 billion over the period from 2014-2019. From it auspicious beginnings, the...

While certain archaea appear to synthesize and/or metabolize fattyacids, the respective pathways still remain obscure. By analyzing the genomic distribution of the key lipid-related enzymes, we were able to identify the likely components of the archaeal pathway of fattyacid metabolism, namely, a combination of the enzymes of bacterial-type β-oxidation of fattyacids (acyl-CoA-dehydrogenase, enoyl-CoA hydratase, and 3-hydroxyacyl-CoA dehydrogenase) with paralogs of the archaeal acetyl-CoA C-acetyltransferase, an enzyme of the mevalonate biosynthesis pathway. These three β-oxidation enzymes working in the reverse direction could potentially catalyze biosynthesis of fattyacids, with paralogs of acetyl-CoA C-acetyltransferase performing addition of C2 fragments. The presence in archaea of the genes for energy-transducing membrane enzyme complexes, such as cytochrome bc complex, cytochrome c oxidase, and diverse rhodopsins, was found to correlate with the presence of the proposed system of fattyacid biosynthesis. We speculate that because these membrane complexes functionally depend on fattyacid chains, their genes could have been acquired via lateral gene transfer from bacteria only by those archaea that already possessed a system of fattyacid biosynthesis. The proposed pathway of archaeal fattyacid metabolism operates in extreme conditions and therefore might be of interest in the context of biofuel production and other industrial applications. PMID:24818264

We have reviewed results from published studies regarding the effects of polyunsaturated fattyacids (PUFA) intake on insulin resistance (IR) in human subjects. Evidence has been gathered from epidemiological, cross-sectional and interventions studies. Increased intake of trans fattyacids (TFA) inc...

Adding alkyl polyglucose (APG) into an anaerobic treatment system of waste activated sludge (WAS) was reported to remarkably improve the production of short-chain fattyacids (SCFAs), especially propionic acid via simultaneously accelerating solubilization and hydrolysis, enhancing acidification, inhibiting methanogenesis and balancing carbon to nitrogen (C/N) ratio of substrate. Not only the production of SCFAs, especially propionic acid, was significantly improved by APG, but also the feasible operation time was shortened. The SCFAs yield at 0.3 g APG per gram of total suspended solids (TSS) within 4 d was 2988 ± 60 mg chemical oxygen demand (COD) per liter, much higher than that those from sole WAS or sole WAS plus sole APG. The corresponding yield of propionic acid was 1312 ± 25 mg COD/L, 7.9-fold of sole WAS. Mechanism investigation showed that during anaerobic treatment of WAS in the presence of APG both the solubilization and hydrolysis were accelerated and the acidification was enhanced, while the methanogenesis was inhibited. Moreover, the activities of key enzymes involved in WAS hydrolysis and acidification were improved through the adjustment of C/N ratio of substrates with APG. The abundance of microorganisms responsible for organic compounds hydrolysis and SCFAs production was also observed to be greatly enhanced with APG via 454 high-throughput pyrosequencing analysis. PMID:25697695

We previously reported that high-intensity exercise training significantly increased citrate synthase (CS) activity, a marker of oxidative enzyme, in rat skeletal muscle to a level equaling that attained after low-intensity prolonged exercise training (Terada et al., J Appl Physiol 90: 2019-2024, 2001). Since mitochondrial oxidative enzymes and fattyacid oxidation (FAO) enzymes are often increased simultaneously, we assessed the effect of high-intensity intermittent swimming training on FAO enzyme activity in rat skeletal muscle. Male Sprague-Dawley rats (3 to 4 weeks old) were assigned to a 10-day period of high-intensity intermittent exercise training (HIT), low-intensity prolonged exercise training (LIT), or sedentary control conditions. In the HIT group, the rats repeated fourteen 20 s swimming sessions with a weight equivalent to 14-16% of their body weight. Between the exercise sessions, a 10 s pause was allowed. Rats in the LIT group swam 6 h/day in two 3 h sessions separated by 45 min of rest. CS activity in the triceps muscle of rats in the HIT and LIT groups was significantly higher than that in the control rats by 36 and 39%, respectively. Furthermore, 3-beta hydroxyacyl-CoA dehydrogenase (HAD) activity, an important enzyme in the FAO pathway in skeletal muscle, was higher in the two training groups than in the control rats (HIT: 100%, LIT: 88%). No significant difference in HAD activity was observed between the two training groups. In conclusion, the present investigation demonstrated that high-intensity intermittent swimming training elevated FAO enzyme activity in rat skeletal muscle to a level similar to that attained after 6 h of low-intensity prolonged swimming exercise training. PMID:15040848

PPARδ (peroxisome proliferator-activated receptor δ) is a regulator of lipid metabolism and has been shown to induce fattyacid oxidation (FAO). PPARδ transgenic and knock-out mice indicate an involvement of PPARδ in regulating mitochondrial biogenesis and oxidative capacity; however, the precise mechanisms by which PPARδ regulates these pathways in skeletal muscle remain unclear. In this study, we determined the effect of selective PPARδ agonism with the synthetic ligand, GW501516, on FAO and mitochondrial gene expression in vitro and in vivo. Our results show that activation of PPARδ by GW501516 led to a robust increase in mRNA levels of key lipid metabolism genes. Mitochondrial gene expression and function were not induced under the same conditions. Additionally, the activation of Pdk4 transcription by PPARδ was coactivated by PGC-1α. PGC-1α, but not PGC-1β, was essential for full activation of Cpt-1b and Pdk4 gene expression via PPARδ agonism. Furthermore, the induction of FAO by PPARδ agonism was completely abolished in the absence of both PGC-1α and PGC-1β. Conversely, PGC-1α-driven FAO was independent of PPARδ. Neither GW501516 treatment nor knockdown of PPARδ affects PGC-1α-induced mitochondrial gene expression in primary myotubes. These results demonstrate that pharmacological activation of PPARδ induces FAO via PGC-1α. However, PPARδ agonism does not induce mitochondrial gene expression and function. PGC-1α-induced FAO and mitochondrial biogenesis appear to be independent of PPARδ. PMID:19435887

Epoxygenated fattyacids (EpFAs), which are lipid mediators produced by cytochrome P450 epoxygenases from polyunsaturated fattyacids, are important signaling molecules known to regulate various biological processes including inflammation, pain and angiogenesis. The EpFAs are further metabolized by soluble epoxide hydrolase (sEH) to form fattyacid diols which are usually less-active. Pharmacological inhibitors of sEH that stabilize endogenous EpFAs are being considered for human clinical uses. Here we review the biology of ω-3 and ω-6 EpFAs on inflammation, pain, angiogenesis and tumorigenesis. PMID:24345640

A time-course feeding trial was conducted for 120 days on juvenile channel catfish (Ictalurus punctatus) to study the effects of diets differing in oil source (fish oil or soy oil) and supplementation with a commercial probiotic. Relative levels of Δ6-fattyacid desaturase (Δ6-FAD) and fattyacid elongase (FAE) expression were assessed in brain and liver tissues. Both genes showed similar expression levels in all groups studied. Fish weight-to-length relationships were evaluated using polynomial regression analyses, which identified a burst in weight and length in the channel catfish on day 105 of treatment; this increase was related to an increase in gene expression. Mid-intestinal lactic acid bacterium (LAB) count was determined according to morphological and biochemical criteria using API strips. There was no indication that intestinal LAB count was affected by the modified diets. The Cunningham glass adherence method was applied to evaluate phagocytic cell activity in peripheral blood. Reactive oxygen species (ROS) generation was assessed through the respiratory burst activity of spleen macrophages by the NBT reduction test. Probiotic-supplemented diets provided a good substrate for innate immune system function; the phagocytic index was significantly enhanced in fish fed soy oil and the probiotic, and at the end of the experimental period, ROS production increased in fish fed soy oil. The substitution of fish oil by soy oil is recommended for food formulation and will contribute to promoting sustainable aquaculture. Probiotics are also recommended for channel catfish farming as they may act as immunonutrients. PMID:26400353

The liver plays a central role in the response to fasting. The hormonal profile in this condition, low insulin, and high concentrations of glucagon in plasma, induce the release of large amounts of fattyacids from adipose tissue. Prolonged starvation can therefore induce a dramatic change in the fattyacid oxidative capacity of liver metabolism. Modulation of gene expression by PPARalpha plays a crucial role in this response. While a major role for PPARalpha in the liver is to produce ketone bodies as fuel through beta-oxidation for peripheral tissues during fast, its participation in the control of CPT1A, the rate-limiting step of the pathway, remains controversial. Using Web-based software (VISTA) combining transcription factor binding site database searches with comparative sequence analyses, we have localized a conserved functional PPAR responsive element downstream of the transcriptional start site of the human CPT1A gene. We have shown that this sequence is fundamental for fattyacids or PGC1-induced transcriptional activation of the CPT1A gene. These results corroborate the hypothesis that PPARalpha regulates the limiting step in the oxidation of fattyacids in liver mitochondria. PMID:16271724

Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals previously implicated in hyperglycemia-induced vascular damage and inactivated 2 important antiatherogenic enzymes, prostacyclin synthase and eNOS. In 2 nondiabetic rodent models — insulin-resistant, obese Zucker (fa/fa) rats and high-fat diet–induced insulin-resistant mice — inactivation of prostacyclin synthase and eNOS was prevented by inhibition of FFA release from adipose tissue; by inhibition of the rate-limiting enzyme for fattyacid oxidation in mitochondria, carnitine palmitoyltransferase I; and by reduction of superoxide levels. These studies identify what we believe to be a novel mechanism contributing to the accelerated atherogenesis and increased cardiovascular disease risk occurring in people with insulin resistance. PMID:16528409

Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fattyacids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

Saw palmetto supplements are one of the most commonly consumed supplements by men with prostate cancer and/or benign prostatic hyperplasia (BPH). Some studies have found significant improvements in BPH and lower urinary tract symptoms (LUTS) with saw palmetto supplementation, whereas others found no benefits. The variation in the efficacy in these trials may be a result of differences in the putative active components, fattyacids and phytosterols, of the saw palmetto supplements. To this end, we quantified the major fattyacids (laurate, myristate, palmitate, stearate, oleate, linoleate) and phytosterols (campesterol, stigmasterol, β-sitosterol) in 20 commercially available saw palmetto supplements using GC-FID and GC-MS, respectively. Samples were classified into liquids, powders, dried berries, and tinctures. Liquid saw palmetto supplements contained significantly higher (p < 0.05) concentrations of total fattyacids (908.5 mg/g), individual fattyacids, total phytosterols (2.04 mg/g), and individual phytosterols, than the other supplement categories. Powders contained significantly higher (p < 0.05) concentrations of total fattyacids than tinctures, which contain negligible amounts of fattyacids (46.3 mg/g) and phytosterols (0.10 mg/g). Our findings suggest that liquid saw palmetto supplements may be the best choice for individuals who want to take a saw palmetto supplement with the highest concentrations of both fattyacids and phytosterols. PMID:24067389

A fundamental feature of the life history of true seals, bears and baleen whales is lactation while fasting. This study examined the mobilization of fattyacids from blubber and their subsequent partitioning into maternal metabolism and milk production in northern elephant seals (Mirounga angustirostris). The fattyacid composition of blubber and milk was measured in both early and late lactation. Proportions of fattyacids in milk and blubber were found to display a high degree of similarity both early and late in lactation. Seals mobilized an enormous amount of lipid (~66 kg in 17 days), but thermoregulatory fattyacids, those that remain fluid at low temperatures, were relatively conserved in the outer blubber layer. Despite the stratification, the pattern of mobilization of specific fattyacids conforms to biochemical predictions. Long chain (>20C) monounsaturated fattyacids (MUFAs) were the least mobilized from blubber and the only class of fattyacids that showed a proportional increase in milk in late lactation. Polyunsaturated fattyacids (PUFAs) and saturated fattyacids (SFAs) were more mobilized from the blubber, but neither proportion increased in milk at late lactation. These data suggest that of the long chain MUFA mobilized, the majority is directed to milk synthesis. The mother may preferentially use PUFA and SFA for her own metabolism, decreasing the availability for deposition into milk. The potential impacts of milk fattyacid delivery on pup diving development and thermoregulation are exciting avenues for exploration. PMID:24126964

Fattyacid ethyl esters (FAEEs) are a form of biodiesel that can be microbially produced via a transesterification reaction of fattyacids with ethanol. The titer of microbially produced FAEEs can be greatly reduced by unbalanced metabolism and an insufficient supply of fattyacids, resulting in a commercially inviable process. Here, we report on a pathway engineering strategy in Saccharomyces cerevisiae for enhancing the titer of microbially produced FAEEs by providing the cells with an orthogonal route for fattyacid synthesis. The fattyacids generated from this heterologous pathway would supply the FAEE production, safeguarding endogenous fattyacids for cellular metabolism and growth. We investigated the heterologous expression of a Type-I fattyacid synthase (FAS) from Brevibacterium ammoniagenes coupled with WS/DGAT, the wax ester synthase/acyl-coenzyme that catalyzes the transesterification reaction with ethanol. Strains harboring the orthologous fattyacid synthesis yielded a 6.3-fold increase in FAEE titer compared to strains without the heterologous FAS. Variations in fattyacid chain length and degree of saturation can affect the quality of the biodiesel; therefore, we also investigated the diversity of the fattyacid production profile of FAS enzymes from other Actinomyces organisms. PMID:25594225

Short-chain fattyacid (SCFA) production from waste activated sludge (WAS) anaerobic fermentation is often limited by the slow hydrolysis rate and poor substrate availability, thus a long fermentation time is required. This paper reports a new pretreatment approach, i.e., using free nitrous acid (FNA) to pretreat sludge, for significantly enhanced SCFA production. Experimental results showed the highest SCFA production occurred at 1.8 mg FNA/L with time of day 6, which was 3.7-fold of the blank at fermentation time of day 12. Mechanism studies revealed that FNA pretreatment accelerated disruption of both extracellular polymeric substances and cell envelope. It was also found that FNA pretreatment benefited hydrolysis and acidification processes but inhibited the activities of methanogens, thereby promoting the yield of SCFA. In addition, the FNA pretreatment substantially stimulated the activities of key enzymes responsible for hydrolysis and acidification, which were consistent with the improvement of solubilization, hydrolysis and acidification of WAS anaerobic fermentation. PMID:26363316

FBI-1 (Pokemon/ZBTB7A) is a proto-oncogenic transcription factor of the BTB/POZ (bric-à-brac, tramtrack, and broad complex and pox virus zinc finger) domain family. Recent evidence suggested that FBI-1 might be involved in adipogenic gene expression. Coincidentally, expression of FBI-1 and fatty-acid synthase (FASN) genes are often increased in cancer and immortalized cells. Both FBI-1 and FASN are important in cancer cell proliferation. SREBP-1 is a major regulator of many adipogenic genes, and FBI-1 and SREBP-1 (sterol-responsive element (SRE)-binding protein 1) interact with each other directly via their DNA binding domains. FBI-1 enhanced the transcriptional activation of SREBP-1 on responsive promoters, pGL2-6x(SRE)-Luc and FASN gene. FBI-1 and SREBP-1 synergistically activate transcription of the FASN gene by acting on the proximal GC-box and SRE/E-box. FBI-1, Sp1, and SREBP-1 can bind to all three SRE, GC-box, and SRE/E-box. Binding competition among the three transcription factors on the GC-box and SRE/E-box appears important in the transcription regulation. FBI-1 is apparently changing the binding pattern of Sp1 and SREBP-1 on the two elements in the presence of induced SREBP-1 and drives more Sp1 binding to the proximal promoter with less of an effect on SREBP-1 binding. The changes induced by FBI-1 appear critical in the synergistic transcription activation. The molecular mechanism revealed provides insight into how proto-oncogene FBI-1 may attack the cellular regulatory mechanism of FASN gene expression to provide more phospholipid membrane components needed for rapid cancer cell proliferation. PMID:18682402

During de novo fattyacid synthesis in sunflower seeds, saturated fattyacid production is influenced by the competition between the enzymes of the principal pathways and the saturated acyl-ACP thioesterases. Genetic backgrounds with more efficient saturated acyl-ACP thioesterase alleles only express their phenotypic effects when the alleles for the enzymes in the main pathway are less efficient. For this reason, we studied the incorporation of [2-(14)C]acetate into the lipids of developing sunflower seeds (Helianthus annuus L.) from several mutant lines in vivo. The labelling of different triacylglycerol fattyacids in different oilseed mutants reflects the fattyacid composition of the seed and supports the channelling theory of fattyacid biosynthesis. Incubation with methyl viologen diminished the conversion of stearoyl-ACP to oleoyl-ACP in vivo through a decrease in the available reductant power. In turn, this led to the accumulation of stearoyl-ACP to the levels detected in seeds from high stearic acid mutants. The concomitant reduction of oleoyl-ACP content inside the plastid allowed us to study the activity of acyl-ACP thioesterases on saturated fattyacids. In these mutants, we verified that the accumulation of saturated fattyacids requires efficient thioesterase activity on saturated-ACPs. By studying the effects of cerulenin on the in vivo incorporation of [2-(14)C]acetate into lipids and on the in vitro activity of beta-ketoacyl-ACP synthase II, we found that elongation to very long chain fattyacids can occur both inside and outside of the plastid in sunflower seeds. PMID:16500723

A fundamental ultrastructural feature shared by the spirochetal pathogens Treponema pallidum subsp. pallidum (T. pallidum) and Borrelia burgdorferi, the etiological agents of venereal syphilis and Lyme disease, respectively, is that their most abundant membrane proteins contain covalently attached fattyacids. In this study, we identified the fattyacids covalently bound to lipoproteins of B. burgdorferi and T. pallidum and examined potential acyl donors to these molecules. Palmitate was the predominant fattyacid of both B. burgdorferi and T. pallidum lipoproteins. T. pallidum lipoproteins also contained substantial amounts of stearate, a fattyacid not typically prevalent in prokaryotic lipoproteins. In both spirochetes, the fattyacids of cellular lipids differed from those of their respective lipoproteins. To characterize phospholipids in these organisms, spirochetes were metabolically labeled with [3H]palmitate or [3H]oleate; B. burgdorferi contained only phosphatidylglycerol and phosphatidylcholine, while T. pallidum contained phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and cardiolipin. Although palmitate predominated in the lipoproteins, there were no apparent differences in the incorporation of these two fattyacids into phospholipids (putative acyl donors). Phospholipase A1 and A2 digestion of phosphatidylcholine from B. burgdorferi and T. pallidum labeled with either [3H]palmitate or [3H]oleate also revealed that neither fattyacid was incorporated preferentially into the 1 and 2 positions (potential acyl donor sites) of the glycerol backbone. The combined findings suggest that fattyacid utilization during lipoprotein synthesis is determined largely by the fattyacid specificities of the lipoprotein acyl transferases. These findings also provide the basis for ongoing efforts to elucidate the relationship between lipoprotein acylation and the physiological functions and inflammatory

Omega-3 fattyacids are essential and can only be obtained from the diet. The requirements during pregnancy have not been established, but likely exceed that of a nonpregnant state. Omega-3 fattyacids are critical for fetal neurodevelopment and may be important for the timing of gestation and birth weight as well. Most pregnant women likely do not get enough omega-3 fattyacids because the major dietary source, seafood, is restricted to 2 servings a week. For pregnant women to obtain adequate omega-3 fattyacids, a variety of sources should be consumed: vegetable oils, 2 low-mercury fish servings a week, and supplements (fish oil or algae-based docosahexaenoic acid). PMID:19173020

Fattyacids are aliphatic monocarboxylic acids. They are classified as saturated, monounsaturated, or polyunsaturated fattyacids depending upon the number of double bonds in the carbon chain. Saturated fattyacids have no double bonds, monounsaturated fattyacids have 1 double bond, and polyunsat...

Populations in Western countries consume an excess of polyunsaturated fattyacids (PUFA), even during pregnancy. Since (n-6) PUFA is critical for brain development, we studied whether a high maternal consumption of this fattyacid alters offsprings' affective-like behaviors and (n-6) PUFA-induced protein kinase C (PKC) activity in the brain. Three different strains of pregnant mice were fed isocaloric diets containing either 16% (control) or 43% (high) energy derived from fat high in (n-6) PUFA (corn oil: Balb/c and CD-1 mice, or soybean oil: C3H mice) throughout gestation. From birth onward dams and offspring were fed a nonpurified diet containing 12% energy from a variety of fats. Two- to 12-month-old female and male offspring of dams exposed to a high (n-6) PUFA diet during pregnancy were significantly more active in an open field, more aggressive in the resident-intruder test and spent less time immobile in the swim test than offspring of dams exposed to a control (n-6) PUFA diet. Significantly greater PKC activity in the hypothalamus and moderately less PKC activity in the whole brain (P = 0.10) were seen in the 2-month-old female and male high (n-6) PUFA offspring compared to controls. Our findings indicate that in utero exposure to a high (n-6) PUFA diet subsequently increases locomotor activity and aggression, and reduces immobility in the swim test. The mechanism mediating these effects may be linked to an increased PKC activity in the hypothalamus. PMID:9868200

Fattyacid composition of the diet may be essential to the development of breast cancer. We studied the ability of several fattyacids of serum total lipids to predict breast cancer incidence in a case-control study nested within a longitudinal population study. The proportions of fattyacids in serum total lipids were determined from stored serum samples collected at baseline for 127 incident breast cancer cases and 242 matched controls. Women with a higher proportion of total polyunsaturated fattyacids (PUFAs) in serum had a reduced risk of breast cancer. The odds ratio (OR) between the highest and lowest tertiles of serum PUFA was 0.31 (95% confidence interval, CI = 0.12-0.77). This association was mainly due to n-6 PUFAs and especially to linoleic acid. The ORs were 0.35 (CI = 0.14-0.84) and 0.29 (CI = 0.12-0.73), respectively. Of the monounsaturated fattyacids (MUFAs), higher trans-11-18:1 levels were related to an increased breast cancer risk (OR = 3.69, CI = 1.35-10.06). The association was stronger in postmenopausal than in premenopausal women. The present study suggests that higher serum proportions of the n-6 PUFA linoleic acid and lower proportions of the MUFA trans-11-18:1 fattyacid predict a reduced incidence of breast cancer. PMID:12881010

The Cytochrome P450 4 (CYP4) family of enzymes in humans is comprised of thirteen isozymes that typically catalyze the ω-oxidation of endogenous fattyacids and eicosanoids. Several CYP4 enzymes can biosynthesize 20-hydroxyeicosatetraenoic acid or 20-HETE, an important signaling eicosanoid involved in regulation of vascular tone and kidney reabsorption. Additionally, accumulation of certain fattyacids is a hallmark of the rare genetic disorders, Refsum disease and X-ALD. Therefore, modulation of CYP4 enzyme activity, either by inhibition or induction, is a potential strategy for drug discovery. Here we review the substrate specificities, sites of expression, genetic regulation, and inhibition by exogenous chemicals of the human CYP4 enzymes, and discuss the targeting of CYP4 enzymes in the development of new treatments for hypertension, stroke, certain cancers and the fattyacid-linked orphan diseases. PMID:23688133

These studies were conducted to assess the relationship between visceral adipose tissue free fattyacid (FFA) release and splanchnic FFA release. Steady-state splanchnic bed palmitate ([9,10-(3)H]palmitate) kinetics were determined from 14 sampling intervals from eight dogs with chronic indwelling arterial, portal vein, and hepatic vein catheters. We tested a model designed to predict the proportion of FFAs delivered to the liver from visceral fat by use of hepatic vein data. The model predicted that 15 +/- 2% of hepatic palmitate delivery originated from visceral lipolysis, which was greater (P = 0.004) than the 11 +/- 2% actually observed. There was a good relationship (r(2) = 0.63) between the predicted and observed hepatic palmitate delivery values, but the model overestimated visceral FFA release more at lower than at higher palmitate concentrations. The discrepancy could be due to differential uptake of FFAs arriving from the arterial vs. the portal vein or to release of FFAs in the hepatic circulatory bed. Splanchnic FFA release measured using hepatic vein samples was strongly related to visceral adipose tissue FFA release into the portal vein. This finding suggests that splanchnic FFA release is a good indicator of visceral adipose tissue lipolysis. PMID:12736157

Apical membrane Cl^- channels control the rate of transepithelial Cl^- secretion in airway epithelia. cAMP-dependent protein kinase and protein kinase C regulate Cl^- channels by phosphorylation; in cystic fibrosis cells, phosphorylation-dependent activation of Cl^- channels is defective. Another important signaling system involves arachidonic acid, which is released from cell membranes during receptor-mediated stimulation. Here we report that arachidonic acid reversibly inhibited apical membrane Cl^- channels in cell-free patches of membrane. Arachidonic acid itself inhibited the channel and not a cyclooxygenase or lipoxygenase metabolite because (i) inhibitors of these enzymes did not block the response, (ii) fattyacids that are not substrates for the enzymes had the same effect as arachidonic acid, and (iii) metabolites of arachidonic acid did not inhibit the channel. Inhibition occurred only when fattyacids were added to the cytosolic surface of the membrane patch. Unsaturated fattyacids were more potent than saturated fattyacids. Arachidonic acid inhibited Cl^- channels from both normal and cystic fibrosis cells. These results suggest that fattyacids directly inhibit apical membrane Cl^- channels in airway epithelial cells.

Polyunsaturated fattyacids (PUFAs) are important membrane components and precursors of signaling molecules. To investigate the roles of these fattyacids in growth, development, and neurological function in an animal system, we isolated Caenorhabditis elegans mutants deficient in PUFA synthesis by direct analysis of fattyacid composition. C. elegans possesses all the desaturase and elongase activities to synthesize arachidonic acid and eicosapentaenoic acid from saturated fattyacid precursors. In our screen we identified mutants with defects in each fattyacid desaturation and elongation step of the PUFA biosynthetic pathway. The fattyacid compositions of the mutants reveal the substrate preferences of the desaturase and elongase enzymes and clearly demarcate the steps of this pathway. The mutants show that C. elegans does not require n3 or Δ5-unsaturated PUFAs for normal development under laboratory conditions. However, mutants with more severe PUFA deficiencies display growth and neurological defects. The mutants provide tools for investigating the roles of PUFAs in membrane biology and cell function in this animal model. PMID:11972048

Jatropha curcas, a tropical plant, has great potential commercial relevance as its seeds have high oil content. The seeds can be processed into high-quality biofuel producing seed cake as a byproduct. The seed cake, however, has not gotten much attention toward its potential usefulness. This work was aimed to determine the antioxidant activity of different fractions of a protein hydrolysate from J. curcas seed cake and to elucidate the molecular structures of the antioxidants. Seed cake was first processed into crude protein isolate and the protein was hydrolyzed by Neutrase. The hydrolysate obtained from 1 h of Neutrase hydrolysis showed the strongest antioxidant activity against DPPH radical (2,2-diphenyl-1-picrylhydrazyl). After a purification series of protein hydrolysate by liquid chromatography, chemicals acting as DPPH radical inhibitors were found to be a mixture of fattyacids, fattyacid derivatives, and a small amount of peptides characterized by mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. PMID:24191657

Plasma profile of fattyacids was examined in a group of children consisting of 7 vegans, 15 lactoovovegetarians and 10 semivegetarians. The children were 11-15 years old and the average period of alternative nutrition was 3.4 years. The results were compared with a group of 19 omnivores that constituted an average sample with respect to biochemical and hematological parameters from a larger study of health and nutritional status of children in Slovakia. Alternative nutrition groups had significantly lower values of saturated fattyacids. The content of oleic acid was identical to omnivores. A significant increase was observed for linoleic and alpha-linolenic (n-3) acids. The dihomo-gamma-linolenic (n-6) acid and arachidonic (n-6) acid values were comparable to omnivores for all alternative nutrition groups. Values of n-3 polyunsaturated fattyacids in lactoovovegetarians were identical to those of omnivores whereas they were significantly increased in semivegetarians consuming fish twice a week. Due to the total exclusion of animal fats from the diet, vegans had significantly reduced values of palmitoleic acid as well as eicosapentaenoic (n-3) acid and docosahexaenoic (n-3) acid resulting in an increased n-6/n-3 ratio. Values of plasma fattyacids found in alternative nutrition groups can be explained by the higher intake of common vegetable oils (high content of linoleic acid), oils rich in alpha-linolenic acid (cereal germs, soybean oil, walnuts), as well as in n-3 polyunsaturated fattyacids (fish). The results of fattyacids (except n-3 in vegans) and other lipid parameters confirm the beneficial effect of vegetarian nutrition in the prevention of cardiovascular diseases. PMID:9491192

Fattyacid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate β-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate–active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high-throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro. PMID:27559295

Fattyacid synthase (FASN, UniProt ID: P49327) is a multienzyme dimer complex that plays a critical role in lipogenesis. Consequently, this lipogenic enzyme has gained tremendous biomedical importance. The role of FASN and its inhibition is being extensively researched in several clinical conditions, such as cancers, obesity, and diabetes. X-ray crystallographic structures of some of its domains, such as β-ketoacyl synthase, acetyl transacylase, malonyl transacylase, enoyl reductase, β-ketoacyl reductase, and thioesterase, (TE) are already reported. Here, we have attempted an in silico elucidation of the uncrystallized dehydratase (DH) catalytic domain of human FASN. This theoretical model for DH domain was predicted using comparative modeling methods. Different stand-alone tools and servers were used to validate and check the reliability of the predicted models, which suggested it to be a highly plausible model. The stereochemical analysis showed 92.0% residues in favorable region of Ramachandran plot. The initial physiological substrate β-hydroxybutyryl group was docked into active site of DH domain using Glide. The molecular dynamics simulations carried out for 20 ns in apo and holo states indicated the stability and accuracy of the predicted structure in solvated condition. The predicted model provided useful biochemical insights into the substrate-active site binding mechanisms. This model was then used for identifying potential FASN inhibitors using high-throughput virtual screening of the National Cancer Institute database of chemical ligands. The inhibitory efficacy of the top hit ligands was validated by performing molecular dynamics simulation for 20 ns, where in the ligand NSC71039 exhibited good enzyme inhibition characteristics and exhibited dose-dependent anticancer cytotoxicity in retinoblastoma cancer cells in vitro. PMID:27559295

A Serratia rubidaea isolate with wetting activity when grown at 30 but not 37 degrees C was examined for the production of specific lipids. Two novel lipids (rubiwettins R1 and RG1) were isolated and shown to be able to lower the surface tension of saline to 26 mN/m. These lipids were located in extracellular vesicles found in a 30 degrees C culture of S. rubidaea. Chemical structures of these biosurfactants were determined by degradation product analyses, infrared spectroscopy, mass spectrometry, and proton nuclear magnetic resonance spectroscopy. Rubiwettin R1 was proposed to be a mixture of 3-(3'-hydroxytetradecanoyloxy)decanoate, 3-(3'-hydroxyhexadecenoyloxy)decanoate, and minor molecular isomers. The structure of rubiwettin RG1 was proposed to be beta-D-glucopyranosyl 3-(3'-hydroxytetradecanoyloxy)decanoate. The importance of such surface-active exolipids in bacterial occupancy on surfaces was suggested. Images PMID:2345132

Suitability assessment of amaranth sprouts as a new functional food was carried out. The optimisation of sprouting process and the influence of selenium supplementation, in doses 10, 15, and 30 mg/l of selenium as sodium selenite, on amaranth growth and fattyacid profile were examined. Methods such as FRAP, DPPH, polyphenols content and GPX activity were applied to characterize antioxidant potential of seeds and sprouts of four different edible amaranth genera. E. coli, S. aureus, C. albicans were used to evaluate amaranth sprouts antimicrobial properties. Interaction between amaranth sprouts and biological systems was assessed by analysing antibacterial and antifungal properties with a disc diffusion test. The studies proved amaranth sprouts to be potentially attractive as functional food. As confirmed by all the data amaranth sprouts are suitable as a moderate selenium accumulator and are rich in essential fattyacids, especially linoleic and alpha-linolenic acids, which are precursors of long chain polyunsaturated fattyacids. Thus, it opens dietary opportunities for amaranth sprouts. They can also serve as a moderate source of antioxidant compounds. Nevertheless, the experiments revealed neither antibacterial, nor antifungal properties of sprouts. In general, amaranth sprouts biological activity under evaluation has failed to prove to be significantly impacted by selenium fertilization. PMID:26243894

Although the disadvantages of trans fattyacids (TFAs) are widely mentioned, limited data are available on the TFAs contents of Iranian foods, including fast foods. The aim of this study was to quantify the amounts of common fattyacids in several fast foods in Iran, with specific focus on TFAs. The most commonly consumed fast foods in Iran: sausage, calbas, hamburgers and pizzas, were randomly selected seven times from products available in supermarkets and restaurants. Each time a 10 g sample was drawn and prepared for fattyacid analysis. Total and individual fattyacids were quantified according to standard methods by gas chromatography with 60 meter capillary column and flame ionization detector. The most common saturated fattyacids in Iranian fast foods is stearic acid (C18:0) which ranged from 14.0% to 20.9%. Saturated fattyacid content in calbas was significantly higher than that found in other groups. Trans fattyacids constitute almost 23.6% to 30.6% of total fattyacids of these products. The most common TFA in these fast foods was elaidic acid (C18:1 9t). Total cis unsaturated fattyacid content of tested fast foods varied from 25.3%(in sausage) to 46.8(in calbas) with oleic acid (C18:1 9c) followed by linoleic acid (C18:2) being the most common fattyacids in these products. This study showed higher TFAs contents in commercially available fast foods compared to the amounts recommended by dietary guidelines in Iran. Further studies must assess the effects of these fattyacids on human health. PMID:19713177

Oxygenases catalyzing the insertion of oxygen into either aliphatic hydrocarbons or fattyacids have great similarity. There are two classes of oxygenases: monooxygenases and dioxygenases. Dioxygenase inserts both atoms of molecular oxygen into a substrate, whereas monooxygenase incorporates one a...

Starting from 17-hydroxyoleic acid, which is readily available from acid alcoholysis of sophorolipids, several new polyhydroxy fattyacids have been synthesized. These compounds contain from 2 to 5 hydroxy groups, in some instances combined with other functional groups. The added hydroxy groups ca...

This review details the specific needs of women for omega-3 fattyacids, including alpha linoleic acid (ALA) and the very long chain fattyacids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fattyacid (dietary or in capsules) ensures that a woman's adipose tissue contains a reserve of these fattyacids for the developing fetus and the breast-fed newborn infant. This ensures the optimal cerebral and cognitive development of the infant. The presence of large quantities of EPA and DHA in the diet slightly lengthens pregnancy, and improves its quality. Human milk contains both ALA and DHA, unlike that of other mammals. Conditions such as diabetes can alter the fattyacid profile of mother's milk, while certain diets, like those of vegetarians, vegans, or even macrobiotic diets, can have the same effect, if they do not include seafood. ALA, DHA and EPA, are important for preventing ischemic cardiovascular disease in women of all ages. Omega-3 fattyacids can help to prevent the development of certain cancers, particularly those of the breast and colon, and possibly of the uterus and the skin, and are likely to reduce the risk of postpartum depression, manic-depressive psychosis, dementias (Alzheimer's disease and others), hypertension, toxemia, diabetes and, to a certain extend, age-related macular degeneration. Omega-3 fattyacids could play a positive role in the prevention of menstrual syndrome and postmenopausal hot flushes. The normal western diet contains little ALA (less than 50% of the RDA). The only adequate sources are rapeseed oil (canola), walnuts and so-called "omega-3" eggs (similar to wild-type or Cretan eggs). The amounts of EPA and DHA in the diet vary greatly from person to person. The only good sources are fish and seafood, together with "omega-3" eggs. PMID:17254747

The role of trans fattyacids (TFA) present in partially hydrogenated fats widely consumed in food and their link with coronary heart disease has been examined in this review. Most of the studies carried out have been on the effects of TFA on blood-lipid profile. The perceived effects of TFA intake depend on the fat or oil with which they are compared and appears to be in between that of dietary saturated fats and monounsaturated fattyacids. When compared to saturated fat, TFA intake shows lower levels of total and LDL-cholesterol in blood. But when both TFA and saturated fattyacids are compared with cis fattyacids or native unhydrogenated oil, increase in total and LDL-cholesterol are noted. The effects of TFA on HDL-cholesterol and Lp(a) are not clearly established. The undesirable effects of TFA can be overcome by inclusion of essential fattyacids at a minimum of 2 energy per cent level in the diet. The link between trans fattyacid intake and coronary heart disease (CHD) are not unequivocally established. PMID:10650721

... accordance with the following prescribed conditions: (a) They are prepared from lactic acid and fattyacids meeting the requirements of § 172.860(b) and/or oleic acid derived from tall oil fattyacids meeting...

Several studies have reported that lactic acid bacteria may increase the production of free fattyacids by lipolysis of milk fat, though no studies have been found in the literature showing the effect of kefir grains on the composition of fattyacids in milk. In this study the influence of kefir grains from different origins [Rio de Janeiro (AR), Viçosa (AV) e Lavras (AD)], different time of storage, and different fat content on the fattyacid content of cow milk after fermentation was investigated. Fattyacid composition was determined by gas chromatography. Values were considered significantly different when p<0.05. The highest palmitic acid content, which is antimutagenic compost, was seen in AV grain (36.6g/100g fattyacids), which may have contributed to increasing the antimutagenic potential in fermented milk. Higher monounsaturated fattyacid (25.8g/100g fattyacids) and lower saturated fattyacid (72.7g/100g fattyacids) contents were observed in AV, when compared to other grains, due to higher Δ9-desaturase activity (0.31) that improves the nutritional quality of lipids. Higher oleic acid (25.0g/100g fattyacids) and monounsaturated fattyacid (28.2g/100g fattyacids) and lower saturated fattyacid (67.2g/100g fattyacids) contents were found in stored kefir relatively to fermented kefir leading to possible increase of antimutagenic and anticarcinogenic potential and improvement of nutritional quality of lipids in storage milk. Only high-lipidic matrix displayed increase polyunsaturated fattyacids after fermentation. These findings open up new areas of study related to optimizing desaturase activity during fermentation in order to obtaining a fermented product with higher nutritional lipid quality. PMID:26444286

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fattyacid synthase (FASN) catalyzes the last step in fattyacid biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fattyacids by de novo lipogenesis. The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of primary human hepatocytes with fattyacids dose-dependently induced cellular lipid-accumulation and FASN expression, while stimulation with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore, FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for the progression of NAFLD. PMID:20606731

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which starts with simple hepatic steatosis and may progress toward inflammation (nonalcoholic steatohepatitis [NASH]). Fattyacid synthase (FASN) catalyzes the last step in fattyacid biosynthesis, and thus, it is believed to be a major determinant of the maximal hepatic capacity to generate fattyacids by de novo lipogenesis. The aim of this study was to analyze the correlation between hepatic steatosis and inflammation with FASN expression. In vitro incubation of primary human hepatocytes with fattyacids dose-dependently induced cellular lipid-accumulation and FASN expression, while stimulation with TNF did not affect FASN levels. Further, hepatic FASN expression was significantly increased in vivo in a murine model of hepatic steatosis without significant inflammation but not in a murine NASH model as compared to control mice. Also, FASN expression was not increased in mice subjected to bile duct ligation, an experimental model characterized by severe hepatocellular damage and inflammation. Furthermore, FASN expression was analyzed in 102 human control or NAFLD livers applying tissue micro array technology and immunohistochemistry, and correlated significantly with the degree of hepatic steatosis, but not with inflammation or ballooning of hepatocytes. Quantification of FASN mRNA expression in human liver samples confirmed significantly higher FASN levels in hepatic steatosis but not in NASH, and expression of SREBP1, which is the main transcriptional regulator of FASN, paralleled FASN expression levels in human and experimental NAFLD. In conclusion, the transcriptional induction of FASN expression in hepatic steatosis is impaired in NASH, while hepatic inflammation in the absence of steatosis does not affect FASN expression, suggesting that FASN may serve as a new diagnostic marker or therapeutic target for the progression of NAFLD. PMID:20606731

With 45 % or more oil content that contains more than 55 % alpha linolenic (LIN) acid, linseed (Linum usitatissimum L.) is one of the richest plant sources of this essential fattyacid. Fattyacid desaturases 2 (FAD2) and 3 (FAD3) are the main enzymes responsible for the Δ12 and Δ15 desaturation in planta. In linseed, the oilseed morphotype of flax, two paralogous copies, and several alleles exist for each gene. Here, we cloned three alleles of FAD2A, four of FAD2B, six of FAD3A, and seven of FAD3B into a pYES vector and transformed all 20 constructs and an empty construct in yeast. The transformants were induced in the presence of oleic (OLE) acid substrate for FAD2 constructs and linoleic (LIO) acid for FAD3. Conversion rates of OLE acid into LIO acid and LIO acid into LIN acid were measured by gas chromatography. Conversion rate of FAD2 exceeded that of FAD3 enzymes with FAD2B having a conversion rate approximately 10 % higher than FAD2A. All FAD2 isoforms were active, but significant differences existed between isoforms of both FAD2 enzymes. Two FAD3A and three FAD3B isoforms were not functional. Some nonfunctional enzymes resulted from the presence of nonsense mutations causing premature stop codons, but FAD3B-C and FAD3B-F seem to be associated with single amino acid changes. The activity of FAD3A-C was more than fivefold greater than the most common isoform FAD3A-A, while FAD3A-F was fourfold greater. Such isoforms could be incorporated into breeding lines to possibly further increase the proportion of LIN acid in linseed. PMID:24522837

Dysregulation of adrenal glucocorticoid production is increasingly recognized to play a supportive role in the metabolic syndrome although the mechanism is ill defined. The adrenal cytochrome P450 (CYP) enzymes, CYP17 and CYP21, are essential for glucocorticoid synthesis. The omega-3 and omega-6 polyunsaturated fattyacids (PUFA) may ameliorate metabolic syndrome, but it is unknown whether they have direct actions on adrenal CYP steroidogenic enzymes. The aim of this study was to determine whether PUFA modify adrenal glucocorticoid synthesis using isolated porcine microsomes. The enzyme activities of CYP17, CYP21, 11β-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase (H6PDH), and CYP2E1 were measured in intact microsomes treated with fattyacids of disparate saturated bonds. Cortisol production was measured in a cell-free in vitro model. Microsomal lipid composition after arachidonic acid (AA) exposure was determined by sequential window acquisition of all theoretical spectra-mass spectrometry. Results showed that adrenal microsomal CYP21 activity was decreased by docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid, α-linolenic acid, AA, and linoleic acid, and CYP17 activity was inhibited by DPA, DHA, eicosapentaenoic acid, and AA. Inhibition was associated with the number of the PUFA double bonds. Similarly, cortisol production in vitro was decreased by DPA, DHA, and AA. Endoplasmic enzymes with intraluminal activity were unaffected by PUFA. In microsomes exposed to AA, the level of AA or oxidative metabolites of AA in the membrane was not altered. In conclusion, these observations suggest that omega-3 and omega-6 PUFA, especially those with 2 or more double bonds (DPA, DHA, and AA), impede adrenal glucocorticoid production. PMID:26889941

Fattyacids represent an important renewable feedstock for the chemical industry. To enable biotechnological one carbon truncations of fattyacids, the enzymes α-dioxygenase and fatty aldehyde dehydrogenase (FALDH) have to be combined in a two-step process. We expressed an FALDH from V. harveyi in E. coli and characterized its substrate spectrum with a focus on the number and position of double bonds in the fatty aldehyde molecules. Synthesis of the expected fattyacid products was proven by analysis of whole cell biotransformation products. Coexpression of a H(2)O-forming NADPH oxidase (NOX) from Lactobacillus sanfranciscensis led to the implementation of a cofactor regeneration cycle in in vitro oxidation experiments. The presence of NOX in whole cell biotransformations improved reaction velocity but did not result in higher product yields. We could further demonstrate that at least part of the endogenous NAD(P)(+) regeneration capacity in the resting cells results from the respiratory chain. The whole cell catalyst with the high broad range FALDH activity described here is an important biotechnological module for lipid biotransformation processes, especially the shortening of fattyacids. PMID:23180547

Rabbit articular chondrocytes were cultured for 8 h in the presence of various concentrations (5-500 microM) of {sup 14}C oleic, {sup 14}C linoleic, and {sup 3H} arachidonic acids. The radioactive unsaturated fattyacids were incorporated into triacylglycerol (TG) and phosphatidylcholine (PC) in a concentration-dependent manner; more fattyacids were incorporated into TG than into PC, at higher concentrations of extracellular fattyacids. Among these fattyacids, arachidonic acid was incorporated into TG much more than into PC, in spite of a very low concentration of arachidonic acid in TG. After transfer of the labeled cells to maintenance medium, the radioactivity in TG declined rapidly and {sup 3}H arachidonic acid radioactivity in PC increased continuously during the chase time periods. Palmitoyl-unsaturated species were mainly formed in PC when cultured at a concentration of 5 microM of each fattyacid. However, when cultured at 500 microM, unsaturated-unsaturated species, specific for each unsaturated fattyacid were actively formed. These findings indicate that (1) fattyacid composition of TG and PC in articular chondrocytes is influenced by the degree of fattyacid supply, (2) formation and turnover of TG plays a role in fattyacid metabolism of cells, and (3) fattyacid pairing in PC is modulated by extracellular fattyacid concentrations.

Hydroxy and oxo fattyacids were recently found to be produced as intermediates during gut microbial fattyacid metabolism. Lactobacillus plantarum produces these fattyacids from unsaturated fattyacids such as linoleic acid. In this study, we investigated the effects of these gut microbial fattyacid metabolites on the lipogenesis in liver cells. We screened their effect on sterol regulatory element binding protein-1c (SREBP-1c) expression in HepG2 cells treated with a synthetic liver X receptor α (LXRα) agonist (T0901317). The results showed that 10-hydroxy-12(Z)-octadecenoic acid (18:1) (HYA), 10-hydroxy-6(Z),12(Z)-octadecadienoic acid (18:2) (γHYA), 10-oxo-12(Z)-18:1 (KetoA), and 10-oxo-6(Z),12(Z)-18:2 (γKetoA) significantly decreased SREBP-1c mRNA expression induced by T0901317. These fattyacids also downregulated the mRNA expression of lipogenic genes by suppressing LXRα activity and inhibiting SREBP-1 maturation. Oral administration of KetoA, which effectively reduced triacylglycerol accumulation and acetyl-CoA carboxylase 2 (ACC2) expression in HepG2 cells, for 2 weeks significantly decreased Srebp-1c, Scd-1, and Acc2 expression in the liver of mice fed a high-sucrose diet. Our findings suggest that the hypolipidemic effect of the fattyacid metabolites produced by L. plantarum can be exploited in the treatment of cardiovascular diseases or dyslipidemia. PMID:26399511

To investigate the feasibility of milk fattyacids as predictors of onset of luteal activity (OLA), 87 lactations taken from 73 healthy Norwegian Red cattle were surveyed over 2 winter housing seasons. The feasibility of using frozen milk samples for dry-film Fourier transform infrared (FTIR) determination of milk samples was also tested. Morning milk samples were collected thrice weekly (Monday, Wednesday, Friday) for the first 10 wk in milk (WIM). These samples had bronopol (2-bromo-2-nitropropane-1,3-diol) added to them before being frozen at -20°C, thawed, and analyzed by ELISA to determine progesterone concentration and the concentrations of the milk fattyacids C4:0, C14:0, C16:0, C18:0, and cis-9 C18:1 as a proportion of total milk fattyacid content using dry-film FTIR, and averaged by WIM. Onset of luteal activity was defined as the first day that milk progesterone concentrations were >3 ng/mL for 2 successive measurements; the study population was categorized as early (n=47) or late (n=40) OLA, using the median value of 21 DIM as the cutoff. Further milk samples were collected 6 times weekly, from morning and afternoon milkings, these were pooled by WIM, and one proportional sample was analyzed fresh for fat, protein, and lactose content by the dairy company Tine SA, using traditional FTIR spectrography in the wet phase of milk. Daily energy-balance calculations were performed in 42 lactations and averaged by WIM. Animals experiencing late OLA had a more negative energy balance in WIM 1, 3, 4, and 5, with the greatest differences been seen in WIM 3 and 4. A higher proportion of the fattyacids were medium chained, C14:0 and C16:0, in the early than in the late OLA group from WIM 1. In WIM 4, the proportion of total fattyacid content that was C16:0 predicted late OLA, with 74% sensitivity and 80% specificity. The long-chain proportion of the fattyacids C18:0 and cis-9 C18:1 were lower in the early than in the late OLA group. Differences were greatest in

The active α-glucosidase inhibitor compounds in the endophytic fungus Colletotrichum sp. TSC13 were found to be the unsaturated fattyacids (oleic, linoleic and linolenic acids). These compounds have potential as antidiabetic agents. The aim of the present study is to investigate the effects of various media composition on growth (mycelium dry weight) and the fattyacids content (μg mg(-1) mycelium DW) of Colletotrichum sp. TSC13 in relation to its α-glucosidase inhibitory activity. For that purpose, the experiments were set up by varying the carbon and nitrogen sources, metal ions and desaturase and fattyacid synthase inhibitors in the media. Colletotrichum sp. TSC13 grown on potato dextrose broth (PDB) was used as control. The α-glucosidase inhibitory activities were (range from 43.9 ± 2.5 to 88.6 ± 5.2%) at 10 μg mL(-1). This activity seemed to correlate with the unsaturated fattyacids content of the samples. Different sugars as carbon source experiment showed that xylose gave the highest growth (938.7 ± 141.6 mg). However, the highest fattyacids content was obtained from fructose medium which containing linoleic acid (38.8 ± 4.9 μ g mg(-1) DW). Soluble starch gave better growth (672.5 ± 62.3 mg) but very low fattyacids content (2.8 ± 0.1 μg mg(-1) DW) was obtained. Yeast extract was the best nitrogen source. Fattyacids production was better as compared to beef extract and soytone. This is the first report of various media compositions on fattyacids content in Colletotrichum sp. TSC13 in relation to its α-glucosidase inhibitory activity. PMID:26035936

The essential fattyacid (EFA) nutrition of young American alligators (Alligator mississippiensis) was examined by feeding a variety of fats/oils with potential EFA activity. Over a 12-wk period, alligators fed diets containing 2.5 or 5.0% chicken liver oil grew longer and heavier and converted feed to body mass more efficiently than alligators fed other fat/oil combinations that lacked or contained only trace amounts of arachidonic acid [20:4(n-6)]. Alligators fed an EFA-deficient diet (containing only coconut fat as the dietary fat) were the slowest-growing animals and converted feed to body mass least efficiently. However, over a 41-wk feeding period, alligators fed this diet showed no obvious external signs of deficiency other than being reduced in size and unthrifty. Fattyacid composition of heart, liver, muscle, skin and adipose tissue lipids was influenced markedly by dietary fat composition. Tissues varied significantly in response to dietary fat composition. Heart lipids contained the lowest levels of short- and medium-chain fattyacids and the highest levels of arachidonic acid. Arachidonic acid levels were less influenced by diet than were levels of other 20- and 22-carbon polyunsaturated fattyacids. Radiotracer studies indicated that linoleic acid was converted to arachidonic acid in the liver. Nevertheless, tissue arachidonic acid levels also appeared to be maintained by concentration from dietary sources and selective conservation. It appears that a dietary source of arachidonic acid may be required for a maximum rate of growth. PMID:2114472

Angiopoietin-like protein 4 (ANGPTL4/FIAF) has been proposed as a circulating mediator between the gut microbiota and fat storage. Here, we show that transcription and secretion of ANGPTL4 in human T84 and HT29 colon adenocarcinoma cells is highly induced by physiological concentrations of short-chain fattyacids (SCFA). SCFA induce ANGPTL4 by activating the nuclear receptor peroxisome proliferator activated receptor γ (PPARγ), as demonstrated using PPARγ antagonist, PPARγ knockdown, and transactivation assays, which show activation of PPARγ but not PPARα and PPARδ by SCFA. At concentrations required for PPARγ activation and ANGPTL4 induction in colon adenocarcinoma cells, SCFA do not stimulate PPARγ in mouse 3T3-L1 and human SGBS adipocytes, suggesting that SCFA act as selective PPARγ modulators (SPPARM), which is supported by coactivator peptide recruitment assay and structural modeling. Consistent with the notion that fermentation leads to PPAR activation in vivo, feeding mice a diet rich in inulin induced PPAR target genes and pathways in the colon. We conclude that (i) SCFA potently stimulate ANGPTL4 synthesis in human colon adenocarcinoma cells and (ii) SCFA transactivate and bind to PPARγ. Our data point to activation of PPARs as a novel mechanism of gene regulation by SCFA in the colon, in addition to other mechanisms of action of SCFA. PMID:23339868

Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE–luciferase reporter assay. We isolated three monounsaturated fattyacid (MUFA) derivatives as active components, including a new keto-type C18 fattyacid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate–cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched

Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE-luciferase reporter assay. We isolated three monounsaturated fattyacid (MUFA) derivatives as active components, including a new keto-type C18 fattyacid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate-cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched with

Streptococcus mutans, one of the primary causative agents of dental caries in humans, ferments dietary sugars in the mouth to produce organic acids. These acids lower local pH values, resulting in demineralization of the tooth enamel, leading to caries. To survive acidic environments, Strep. mutans employs several adaptive mechanisms, including a shift from saturated to unsaturated fattyacids in membrane phospholipids. PlsX is an acyl-ACP : phosphate transacylase that links the fattyacid synthase II (FASII) pathway to the phospholipid synthesis pathway, and is therefore central to the movement of unsaturated fattyacids into the membrane. Recently, we discovered that plsX is not essential in Strep. mutans. A plsX deletion mutant was not a fattyacid or phospholipid auxotroph. Gas chromatography of fattyacid methyl esters indicated that membrane fattyacid chain length in the plsX deletion strain differed from those detected in the parent strain, UA159. The deletion strain displayed a fattyacid shift similar to WT, but had a higher percentage of unsaturated fattyacids at low pH. The deletion strain survived significantly longer than the parent strain when cultures were subjected to an acid challenge of pH 2.5.The ΔplsX strain also exhibited elevated F-ATPase activity at pH 5.2, compared with the parent. These results indicate that the loss of plsX affects both the fattyacid synthesis pathway and the acid-adaptive response of Strep. mutans. PMID:26850107

White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fattyacids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fattyacid esters of hydroxy fattyacids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans. PMID:27313314

2-Alkynoic fattyacids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC50 = 5.3 ± 0.7 μM. The potency of LdTopIB inhibition follows the trend 2-ODA> 2-HDA> 2-TDA, indicating that the effectiveness of inhibition depends on the fattyacid carbon chain length. All of the studied 2-alkynoic fattyacids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC50 = 11.0 μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC50 = 48.1 μM) and T. brucei rhodesiense (IC50 = 64.5 μM). The antiprotozoal activity of the 2-alkynoic fattyacids, in general, followed the trend 2-ODA> 2-HDA> 2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound. PMID:22932312

Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic to the central region of Chile, induces a severe contact dermatitis in susceptible human beings. The allergen was previously isolated and characterized as a 3-(pentadecyl-10-enyl) catechol, a molecule belonging to the urushiol group of allergens isolated from poison ivy and poison oak plants. Because urushiols are pro-electrophilic haptens, it is believed that the reactive species are generated intracellularly by skin keratinocytes and Langerhans cells. The active species are presumed to modify self proteins which, after proteolytic processing, would generate immunogenic peptides carrying the hapten. The presence of a 15-carbon-length hydrophobic chain should impair antigen presentation of self-modified peptides by class I MHC molecules, either by steric hindrance or by limiting their sorting to the ER lumen. We have proposed that the shortening of the aliphatic chain by beta-oxidation within peroxisomes and/or mitochondria should be a requirement for the antigen presentation process. To test this hypothesis we investigated the effect of drugs that modify the fattyacid metabolism on urushiol-induced contact dermatitis in mice. Clofibrate, a peroxisomal proliferator in mice, increased the immune response to the urushiols from litre by 50%. Conversely, tetradecyl glycidic acid, an inhibitor of the uptake of fattyacids by mitochondria, decreased the hypersensitivity to the hapten. An increase in the level in glutathione by treatment of the animals with 2-oxotiazolidin-4-carboxilic acid lowered the response. Those findings strongly support a role for the fattyacid oxidative metabolism in the processing and activation of urushiols in vivo. PMID:8980288

Background One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as Peroxisome Proliferators Activated Receptors (PPARs) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) are involved in cholesterol homeostasis. FattyAcids are important ligands of PPARα and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fattyacids on the lipid metabolism in foam cells. Methods This study examined effects of c9, t11-Conjugated Linoleic Acid(c9, t11-CLA), Alpha Linolenic Acid (LA), Eicosapentaenoic Acid (EPA) on the PPARα and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells. Results Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular Total Cholesterol, Free Cholesterol, cellular and Estrified Cholesterol concentrations (P ≤ 0.05). CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (P = 0.003). Treatment with EPA increased PPARα mRNA levels (P ≤ 0.001), although CLA, LA had no significant effect on PPARα mRNA expression. Conclusion In conclusion, it seems that different fattyacids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit. PMID:19725980

This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fattyacids in transgenic plants. In addition, the use of genes encoding fattyacid hydroxylases or desaturases to alter the level of lipid fattyacid unsaturation in transgenic plants is described.

This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fattyacids in transgenic plants. In addition, the use of genes encoding fattyacid hydroxylases or desaturases to alter the level of lipid fattyacid unsaturation in transgenic plants is described.

INTRODUCTION This study was designed and conducted to evaluate the effects of vitamin A, C and E supplementation, and omega-3 fattyacid supplementation on the activity of paraoxonase and arylesterase in an experimental model of diabetes mellitus. METHODS A total of 64 male Sprague Dawley® rats, each weighing 250 g, were randomly distributed into four groups: (a) normal control; (b) diabetic control; (c) diabetic with vitamin A, C and E supplementation; and (d) diabetic with omega-3 fattyacid supplementation. The animals were anaesthetised after four weeks of intervention, and paraoxonase and arylesterase activity in blood plasma, and liver and heart homogenates were measured. RESULTS Arylesterase activity in the heart and liver homogenates was significantly lower in the diabetic control group than in the normal control group (p < 0.01). Vitamin A, C and E supplementation, and omega-3 fattyacid supplementation significantly increased liver arylesterase activity (p < 0.05). No significant change was observed in paraoxonase activity and other investigated factors. CONCLUSION Vitamin A, C and E, or omega-3 fattyacid supplementation were found to increase liver arylesterase activity in streptozotocin-induced diabetic rats. These supplements may be potential agents for the treatment of diabetes mellitus complications. PMID:26996784

AIM: To investigate how the saturated and unsaturated fattyacid composition influences the susceptibility of developing acute pancreatitis. METHODS: Primary pancreatic acinar cells were treated with low and high concentrations of different saturated and unsaturated fattyacids, and changes in the cytosolic Ca2+ signal and the expression of protein kinase C (PKC) were measured after treatment. RESULTS: Unsaturated fattyacids at high concentrations, including oleic acid, linoleic acid, palmitoleic acid, docosahexaenoic acid, and arachidonic acid, induced a persistent rise in cytosolic Ca2+ concentrations in acinar cells. Unsaturated fattyacids at low concentrations and saturated fattyacids, including palmitic acid, stearic acid, and triglycerides, at low and high concentrations were unable to induce a rise in Ca2+ concentrations in acinar cells. Unsaturated fattyacids at high concentrations but not saturated fattyacids induced intra-acinar cell trypsin activation and cell damage and increased PKC expression. CONCLUSION: At sufficiently high concentrations, unsaturated fattyacids were able to induce acinar cells injury and promote the development of pancreatitis. Unsaturated fattyacids may play a distinctive role in the pathogenesis of pancreatitis through the activation of PKC family members. PMID:26327761

A recently discovered class of endogenous mammalian lipids, branched fattyacid esters of hydroxy fattyacids (FAHFAs), possesses anti-diabetic and anti-inflammatory activities. Here, we identified and validated carboxyl ester lipase (CEL), a pancreatic enzyme hydrolyzing cholesteryl esters and other dietary lipids, as a FAHFA hydrolase. Variants of CEL have been linked to maturity-onset diabetes of the young, type 8 (MODY8), and to chronic pancreatitis. We tested the FAHFA hydrolysis activity of the CEL MODY8 variant and found a modest increase in activity as compared with that of the normal enzyme. Together, the data suggest that CEL might break down dietary FAHFAs. PMID:27509211

Animal and ecological studies of essential fattyacids suggest that omega-3 fattyacids found in fish oils and omega-6 fattyacids found in vegetable oils may be playing a role in the etiology of breast cancer. Essential fattyacids may modulate breast cancer risk by interacting with prostaglandins, which have immunosuppressive and platelet aggregative capabilities. The fattyacid composition of adipose tissue reflects the dietary consumption of essential fattyacids over a period of years. Biochemical techniques have been used in epidemiological studies to accurately estimate fattyacid consumption. However, analytical epidemiology studies that have used biochemical measurements of adipose tissue fattyacid composition, have not supported a relationship between consumption of these essential fattyacids and breast cancer risk. PMID:7612909

The effect of some fattyacids on the phase behavior of hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer was investigated with special interest in possible difference between saturated and unsaturated fattyacids. The phase behavior of hydrated DPPC bilayer was followed by a differential scanning calorimetry and a Fourier transform infrared spectroscopy. The addition of palmitic acid (PA) increased the bilayer phase transition temperature with the increase of the PA content in the mixture. In addition, DPPC molecules in gel phase bilayer became more rigid in the presence of PA compared with those in the absence of PA. This effect of PA on the phase behavior of hydrated DPPC bilayer is common to other saturated fattyacids, stearic acid, myristic acid, and also to unsaturated fattyacid with trans double bond, elaidic acid. Contrary to these fattyacids, oleic acid (OA), the unsaturated fattyacid with cis double bond in the acyl chain, exhibited quite different behavior. The effect of OA on the bilayer phase transition temperature was rather small, although a slight decrease in the temperature was appreciable. Furthermore, the IR spectral results demonstrated that the perturbing effect of OA on the gel phase bilayer of DPPC was quite small. These results mean that OA does not disturb the hydrated DPPC bilayer significantly. PMID:11269932

The soybean aphid (Aphis glycines Matsumura) is one of the most important insect pests of soybeans in the North-central region of the US. It has been hypothesized that aphids avoid effective defenses by inhibition of jasmonate-regulated plant responses. Given the role fattyacids play in jasmonate-induced plant defenses, we analyzed the fattyacid profile of soybean leaves and seeds from aphid-infested plants. Aphid infestation reduced levels of polyunsaturated fattyacids in leaves with a concomitant increase in palmitic acid. In seeds, a reduction in polyunsaturated fattyacids was associated with an increase in stearic acid and oleic acid. Soybean plants challenged with the brown stem rot fungus or with soybean cyst nematodes did not present changes in fattyacid levels in leaves or seeds, indicating that the changes induced by aphids are not a general response to pests. One of the polyunsaturated fattyacids, linolenic acid, is the precursor of jasmonate; thus, these changes in fattyacid metabolism may be examples of “metabolic hijacking” by the aphid to avoid the induction of effective defenses. Based on the changes in fattyacid levels observed in seeds and leaves, we hypothesize that aphids potentially induce interference in the fattyacid desaturation pathway, likely reducing FAD2 and FAD6 activity that leads to a reduction in polyunsaturated fattyacids. Our data support the idea that aphids block jasmonate-dependent defenses by reduction of the hormone precursor. PMID:26684003

Appropriate activation of CD4(+) T cells is fundamental for efficient initiation and progression of acquired immune responses. Here, we showed that CD4(+) T-cell activation is dependent on changes in membrane n-3 polyunsaturated fattyacids (PUFAs) and is dynamically regulated by the type of signals provided by dendritic cells (DCs). Upon interaction with DCs primed by different concentrations and species of gut bacteria, CD4(+) T cells were activated according to the type of DC stimulus. The levels of CD80 were found to correlate to the levels of expression of CD28 and to the proliferation of CD4(+) T cells, while the presence of CD40 and CD86 on DCs inversely affected inducible costimulator (ICOS) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in CD4(+) T cells. For all DC stimuli, cells high in n-3 PUFAs showed reduced ability to respond to CD28 stimulation, to proliferate, and to express ICOS and CTLA-4. Diminished T-cell receptor (TCR) and CD28 signalling was found to be responsible for n-3 PUFA effects. Thus, the dietary fattyacid composition influences the overall level of CD4(+) T-cell activation induced by DCs, while the priming effect of the DC stimuli modulates CD80, CD86 and CD40 levels, thereby affecting and shaping activation of acquired immunity by differential regulation of proliferation and costimulatory molecule expression in CD4(+) T cells. PMID:19909377

Appropriate activation of CD4+ T cells is fundamental for efficient initiation and progression of acquired immune responses. Here, we showed that CD4+ T-cell activation is dependent on changes in membrane n-3 polyunsaturated fattyacids (PUFAs) and is dynamically regulated by the type of signals provided by dendritic cells (DCs). Upon interaction with DCs primed by different concentrations and species of gut bacteria, CD4+ T cells were activated according to the type of DC stimulus. The levels of CD80 were found to correlate to the levels of expression of CD28 and to the proliferation of CD4+ T cells, while the presence of CD40 and CD86 on DCs inversely affected inducible costimulator (ICOS) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in CD4+ T cells. For all DC stimuli, cells high in n-3 PUFAs showed reduced ability to respond to CD28 stimulation, to proliferate, and to express ICOS and CTLA-4. Diminished T-cell receptor (TCR) and CD28 signalling was found to be responsible for n-3 PUFA effects. Thus, the dietary fattyacid composition influences the overall level of CD4+ T-cell activation induced by DCs, while the priming effect of the DC stimuli modulates CD80, CD86 and CD40 levels, thereby affecting and shaping activation of acquired immunity by differential regulation of proliferation and costimulatory molecule expression in CD4+ T cells. PMID:19909377

We crystallized human liver fattyacid-binding protein (LFABP) in apo, holo, and intermediate states of palmitic acid engagement. Structural snapshots of fattyacid recognition, entry, and docking within LFABP support a heads-in mechanism for ligand entry. Apo-LFABP undergoes structural remodeling, where the first palmitate ingress creates the atomic environment for placement of the second palmitate. These new mechanistic insights will facilitate development of pharmacological agents against LFABP. PMID:21757748

Trans-fattyacids (TFA) have been associated with increased risk of coronary heart disease, by affecting blood lipids and inflammation factors. Current nutrition recommendations emphasise a limitation of dietary TFA intake. The aim of this study was to investigate fattyacid composition in sweet bakery products, with emphasis on TFA, on the Swedish market and compare fattyacid composition over time. Products were sampled in 2001, 2006 and 2007 and analysed for fattyacid composition by using GC. Mean TFA levels were 0.7% in 2007 and 5.9% in 2001 of total fattyacids. In 1995-97, mean TFA level was 14.3%. In 2007, 3 of 41 products had TFA levels above 2% of total fattyacids. TFA content had decreased in this product category, while the proportion of saturated (SFA) and polyunsaturated (PUFA) fattyacids had increased, mostly through increased levels of 16:0 and 18:2 n-6, respectively. The total fat content remained largely unchanged. PMID:25577101

Omega fattyacids are recognized as key nutrients for healthier ageing. Lipases are used to release ω-3 fattyacids from oils for preparing enriched ω-3 fattyacid supplements. However, use of lipases in enrichment of ω-3 fattyacids is limited due to their insufficient specificity for ω-3 fattyacids. In this study use of phospholipase A1 (PLA1), which possesses both sn-1 specific activity on phospholipids and lipase activity, was explored for hydrolysis of ω-3 fattyacids from anchovy oil. Substrate specificity of PLA1 from Thermomyces lenuginosus was initially tested with synthetic p-nitrophenyl esters along with a lipase from Bacillus subtilis (BSL), as a lipase control. Gas chromatographic characterization of the hydrolysate obtained upon treatment of anchovy oil with these enzymes indicated a selective retention of ω-3 fattyacids in the triglyceride fraction by PLA1 and not by BSL. 13C NMR spectroscopy based position analysis of fattyacids in enzyme treated and untreated samples indicated that PLA1 preferably retained ω-3 fattyacids in oil, while saturated fattyacids were hydrolysed irrespective of their position. Hydrolysis of structured triglyceride,1,3-dioleoyl-2-palmitoylglycerol, suggested that both the enzymes hydrolyse the fattyacids at both the positions. The observed discrimination against ω-3 fattyacids by PLA1 appears to be due to its fattyacid selectivity rather than positional specificity. These studies suggest that PLA1 could be used as a potential enzyme for selective concentrationof ω-3 fattyacids. PMID:26978518

Omega fattyacids are recognized as key nutrients for healthier ageing. Lipases are used to release ω-3 fattyacids from oils for preparing enriched ω-3 fattyacid supplements. However, use of lipases in enrichment of ω-3 fattyacids is limited due to their insufficient specificity for ω-3 fattyacids. In this study use of phospholipase A1 (PLA1), which possesses both sn-1 specific activity on phospholipids and lipase activity, was explored for hydrolysis of ω-3 fattyacids from anchovy oil. Substrate specificity of PLA1 from Thermomyces lenuginosus was initially tested with synthetic p-nitrophenyl esters along with a lipase from Bacillus subtilis (BSL), as a lipase control. Gas chromatographic characterization of the hydrolysate obtained upon treatment of anchovy oil with these enzymes indicated a selective retention of ω-3 fattyacids in the triglyceride fraction by PLA1 and not by BSL. 13C NMR spectroscopy based position analysis of fattyacids in enzyme treated and untreated samples indicated that PLA1 preferably retained ω-3 fattyacids in oil, while saturated fattyacids were hydrolysed irrespective of their position. Hydrolysis of structured triglyceride,1,3-dioleoyl-2-palmitoylglycerol, suggested that both the enzymes hydrolyse the fattyacids at both the positions. The observed discrimination against ω-3 fattyacids by PLA1 appears to be due to its fattyacid selectivity rather than positional specificity. These studies suggest that PLA1 could be used as a potential enzyme for selective concentrationof ω-3 fattyacids. PMID:26978518

The effect of long-term oral administration of arachidonic acid (ARA, 240 mg/kg/day) on brain function was assessed for mice maintained on an n-3 fattyacid adequate or deficient diet. The administration of ARA for 13 weeks resulted in an elevation of spontaneous motor activity, or the tendency thereof, in both the n-3 fattyacid adequate and deficient groups. However, the n-3 fattyacid deficient mice that were administered with ARA revealed marked deterioration in motor function in a motor coordination test. In the experiment to investigate changes over time, the motor activity of the ARA-administered group continued to increase mildly in n-3 deficient mice, although that of the control group showed a decrease involving habituation for both diet groups from the second week. The fattyacid composition of the brain at the end of the behavioral experiments indicated an increase in the levels of ARA and other n-6 fattyacids, as well as a decrease in the levels of docosahexaenoic acid. These results suggest that long-term administration of ARA causes an increase of futile spontaneous motor activity and the diminution of motor function by aggravation of n-3 fattyacid deficiency. PMID:25650363

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. The discovery of food components that can ameliorate NAFLD is therefore of interest. Betulinic acid (BA) is a triterpenoid with many pharmacological activities, but the effect of BA on fatty liver is as yet unknown. To explore the possible anti-fatty liver effects and their underlying mechanisms, we used insulin-resistant HepG2 cells, primary rat hepatocytes and liver tissue from ICR mice fed a high-fat diet (HFD). Oil Red O staining revealed that BA significantly suppressed excessive triglyceride accumulation in HepG2 cells and in the livers of mice fed a HFD. Ca(+2)-calmodulin dependent protein kinase kinase (CAMKK) and AMP-activated protein kinase (AMPK) were both activated by BA treatment. In contrast, the protein levels of sterol regulatory element-binding protein 1 (SREBP1), mammalian target of rapamycin (mTOR) and S6 kinase (S6K) were all reduced when hepatocytes were treated with BA for up to 24h. We found that BA activates AMPK via phosphorylation, suppresses SREBP1 mRNA expression, nuclear translocation and repressed SREBP1 target gene expression in HepG2 cells and primary hepatocytes, leading to reduced lipogenesis and lipid accumulation. These effects were completely abolished in the presence of STO-609 (a CAMKK inhibitor) or compound C (an AMPK inhibitor), indicating that the BA-induced reduction in hepatic steatosis was mediated via the CAMKK-AMPK-SREBP1 signaling pathway. Taken together, our results suggest that BA effectively ameliorates intracellular lipid accumulation in liver cells and thus is a potential therapeutic agent for the prevention of fatty liver disease. PMID:23435355

Inflammation is believed to play a central role in many of the chronic diseases that characterize modern society. In the past decade, our understanding of how dietary fats affect our immune system and subsequently our inflammatory status has grown considerably. There are compelling data showing that high-fat meals promote endotoxin [e.g., lipopolysaccharide (LPS)] translocation into the bloodstream, stimulating innate immune cells and leading to a transient postprandial inflammatory response. The nature of this effect is influenced by the amount and type of fat consumed. The role of various dietary constituents, including fats, on gut microflora and subsequent health outcomes in the host is another exciting and novel area of inquiry. The impact of specific fattyacids on inflammation may be central to how dietary fats affect health. Three key fattyacid-inflammation interactions are briefly described. First, the evidence suggests that saturated fattyacids induce inflammation in part by mimicking the actions of LPS. Second, the often-repeated claim that dietary linoleic acid promotes inflammation was not supported in a recent systematic review of the evidence. Third, an explanation is offered for why omega-3 (n-3) polyunsaturated fattyacids are so much less anti-inflammatory in humans than in mice. The article closes with a cautionary tale from the genomic literature that illustrates why extrapolating the results from inflammation studies in mice to humans is problematic. PMID:25979502

Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fattyacid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner. PMID:25847235

Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increased circulating free fattyacids (FFAs) in NAFLD, we hypothesized the involvement of cholangiocyte lipoapoptosis as a mechanism of cellular injury. Here, we demonstrate that the saturated FFAs palmitate and stearate induced robust and rapid cell death in cholangiocytes. Palmitate and stearate induced cholangiocyte lipoapoptosis in a concentration-dependent manner in multiple cholangiocyte-derived cell lines. The mechanism of lipoapoptosis relied on the activation of caspase 3/7 activity. There was also a significant up-regulation of the proapoptotic BH3-containing protein, PUMA. In addition, palmitate-induced cholangiocyte lipoapoptosis involved a time-dependent increase in the nuclear localization of forkhead family of transcription factor 3 (FoxO3). We show evidence for posttranslational modification of FoxO3, including early (6 hours) deacetylation and dephosphorylation that coincide with localization of FoxO3 in the nuclear compartment. By 16 hours, nuclear FoxO3 is both phosphorylated and acetylated. Knockdown studies confirmed that FoxO3 and its downstream target, PUMA, were critical for palmitate- and stearate-induced cholangiocyte lipoapoptosis. Interestingly, cultured cholangiocyte-derived cells did not accumulate appreciable amounts of neutral lipid upon FFA treatment. Conclusion Our data show that the saturated FFAs palmitate and stearate induced cholangiocyte lipoapoptosis by way of caspase activation, nuclear translocation of FoxO3, and increased proapoptotic PUMA expression. These results suggest that cholangiocyte injury may occur through lipoapoptosis in NAFLD and nonalcoholic steatohepatitis patients. PMID:24753158

The general subject of the review is analysis of the effect of technological parameters on the chemoenzymatic epoxidation processes of vegetable oils, fattyacids and alkyl esters of fattyacids. The technological parameters considered include temperature, concentration, amount of hydrogen peroxide relative to the number of unsaturated bonds, the amounts of enzyme catalysts, presence of solvent and amount of free fattyacids. Also chemical reactions accompanying the technological processes are discussed together with different technological options and significance of the products obtained. PMID:26633342

The peripherally restricted fattyacid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAR) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date. PMID:23822179

A variety of fattyacids exists in the diet of humans, in the bloodstream of humans, and in cells and tissues of humans. Fattyacids are energy sources and membrane constituents. They have biological activities that act to influence cell and tissue metabolism, function, and responsiveness to hormonal and other signals. The biological activities may be grouped as regulation of membrane structure and function; regulation of intracellular signaling pathways, transcription factor activity, and gene expression; and regulation of the production of bioactive lipid mediators. Through these effects, fattyacids influence health, well-being, and disease risk. The effects of saturated, cis monounsaturated, ω-6 and ω-3 polyunsaturated, and trans fattyacids are discussed. Although traditionally most interest in the health impact of fattyacids related to cardiovascular disease, it is now clear that fattyacids influence a range of other diseases, including metabolic diseases such as type 2 diabetes, inflammatory diseases, and cancer. Scientists, regulators, and communicators have described the biological effects and the health impacts of fattyacids according to fattyacid class. However, it is now obvious that within any fattyacid class, different members have different actions and effects. Thus, it would seem more appropriate to describe biological effects and health impacts of individual named fattyacids, although it is recognized that this would be a challenge when communicating outside of an academic environment (eg, to consumers). PMID:26177664

Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fattyacids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fattyacids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fattyacids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fattyacids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fattyacids may be exerting their biological action in skeletal muscle. PMID:26610527

For some decades, an increase in propagation of coronary heart disease, obesity, diabetes, tumors and mental disorders has been observed. Consequently, new and effective methods of treatment of these diseases using drugs and diet supplements have been developed. A promising solution is the use of polyunsaturated fattyacids in the treatment of some diseases. These compounds have broad application in prevention of many diseases and are used to support standard therapies. Their activity is connected with participation in metabolic processes regulating biochemical transformations in cells and tissues. Omega-3 fattyacids regulate production of cytokines, increased levels of which may contribute to occurrence of chronic inflammatory diseases, autoaggression of the immunological system, arteriosclerosis or tumor development. These substances exert a beneficial effect on the blood system by improvement of blood circulation and nerve signal transmission. Omega-3 fattyacids reduce the risk of irregular heartbeat, stabilize arterial pressure, and restore balance in cholesterol metabolism disorders. They also play a key role in maintaining physical and mental efficiency; thus administration of these compounds for young children is of great importance. Nevertheless, administration of omega-3 fattyacids in the diet seems to be essential. The purpose of this study is to present the structure and sources of omega-3 and - 6 fattyacids and discuss the problems concerning therapeutic use of these compounds in various disorders. PMID:26206997

Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fattyacids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fattyacids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fattyacids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fattyacids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fattyacids may be exerting their biological action in skeletal muscle. PMID:26610527

Glutamine, a multifunctional amino acid, functions in nutrient metabolism, energy balance, apoptosis, and cell proliferation. Lipid is an important nutrient and controls a broad range of physiological processes. Previous studies have demonstrated that glutamine can affect lipolysis and lipogenesis, but the effect of glutamine on the detailed lipid metabolism remains incompletely understood. Here, we applied the quantitative proteomics approach to estimate the relative abundance of proteins in HepG2 cells treated by glutamine deprivation. The results showed that there were 212 differentially abundant proteins in response to glutamine deprivation, including 150 significantly increased proteins and 62 significantly decreased proteins. Interestingly, functional classification showed that 43 differentially abundant proteins were related to lipid metabolism. Further bioinformatics analysis and western blotting validation revealed that lipid accumulation may be affected by β-oxidation of fattyacid induced by glutamine deprivation in HepG2 cells. Together, our results may provide the potential for regulating lipid metabolism by glutamine in animal production and human nutrition. The MS data have been deposited to the ProteomeXchange Consortium with identifier PXD003387. PMID:26837383

Fattyacids (n-alcanoic acids) are common compounds in numerous anthropogenic and natural emissions. According to Rogge et al. (1993), catalyst-equipped automobiles emitted more than 600 μg km-1 of fattyacids which was over 50% of all identified organics in fine aerosol emissions. Coal burning produces fattyacids ranging from about 1700 mg kg-1 for bituminous coal to over 10000 mg kg-1 for lignite (Oros and Simoneit, 2000). Similarly, biomass burning is an important source for aerosol fattyacids. They are the major identified compound group in deciduous tree smoke, their total emission factor being measured as 1589 mg kg-1 which was 56% of all identified organic compounds (Oros and Simoneit, 2001a). Large amounts of fattyacid are also emitted from burning of conifer trees and grass (Oros and Simoneit, 2001a; Simoneit, 2002). Fattyacids have been reported to be major constituents of marine aerosols in many investigations (Barger and Garrett, 1976; Gagosian et. al, 1981; Sicre et al., 1990; Stephanou, 1992). It has been suggested that as the marine aerosol particles form, they acquire a coating of organic surfactants (Blanchard, 1964; Gill et al., 1983; Middlebrook et al., 1998; Ellison et al., 1999). Amphiphilic molecules, including lipids, can be assembled as monomolecular layers at air/water interfaces as well as transported to a solid support. Recently, we could show by time-of-flight secondary ion mass spectrometry that fattyacids are important ingredients of the outermost surface layer of the sea-salt aerosol particles (Tervahattu et al., 2002). In their TOF-SIMS studies on the surface composition of atmospheric aerosols, Peterson and Tyler (2002) found fattyacids on the surface of Montana forest fire particles. In this work we have studied by TOF-SIMS the surface chemical composition of aerosol particles emitted from field fires in the Baltic and other East European countries and transported to Finland as well as aerosol particles transported from

Mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) controls the first step of triacylglycerol (TAG) synthesis and is critical to the understanding of chronic metabolic disorders such as primary nonalcoholic fatty liver disease (NAFLD). Anthocyanin, a large group of polyphenols, was negatively correlated with hepatic lipid accumulation, but its impact on mtGPAT1 activity and NAFLD has yet to be determined. Hepatoma cell lines and KKAy mice were used to investigate the impact of anthocyanin on high glucose-induced mtGPAT1 activation and hepatic steatosis. Treatment with anthocyanin cyanidin-3-O-β-glucoside (Cy-3-g) reduced high glucose-induced GPAT1 activity through the prevention of mtGPAT1 translocation from the endoplasmic reticulum to the outer mitochondrial membrane (OMM), thereby suppressing intracellular de novo lipid synthesis. Cy-3-g treatment also increased protein kinase C ζ phosphorylation and membrane translocation in order to phosphorylate the mtF0F1-ATPase β-subunit, reducing its enzymatic activity and thus inhibiting mtGPAT1 activation. In vivo studies further showed that Cy-3-g treatment significantly decreases hepatic mtGPAT1 activity and its presence in OMM isolated from livers, thus ameliorating hepatic steatosis in diabetic KKAy mice. Our findings reveal a novel mechanism by which anthocyanin regulates lipogenesis and thereby inhibits hepatic steatosis, suggesting its potential therapeutic application in diabetes and related steatotic liver diseases. PMID:21343633

Cyclopropane fattyacids (CPA) have been found in certain gymnosperms, Malvales, Litchi and other Sapindales. The presence of their unique strained ring structures confers physical and chemical properties characteristic of unsaturated fattyacids with the oxidative stability displayed by saturated fattyacids making them of considerable industrial interest. While cyclopropenoid fattyacids (CPE) are well-known inhibitors of fattyacid desaturation in animals, CPE can also inhibit the stearoyl-CoA desaturase and interfere with the maturation and reproduction of some insect species suggesting that in addition to their traditional role as storage lipids, CPE can contribute to the protection of plants from herbivory. Three genes encoding cyclopropane synthase homologues GhCPS1, GhCPS2 and GhCPS3 were identified in cotton. Determination of gene transcript abundance revealed differences among the expression of GhCPS1, 2 and 3 showing high, intermediate and low levels, respectively, of transcripts in roots and stems; whereas GhCPS1 and 2 are both expressed at low levels in seeds. Analyses of fattyacid composition in different tissues indicate that the expression patterns of GhCPS1 and 2 correlate with cyclic fattyacid (CFA) distribution. Deletion of the N-terminal oxidase domain lowered GhCPS's ability to produce cyclopropane fattyacid by approximately 70%. GhCPS1 and 2, but not 3 resulted in the production of cyclopropane fattyacids upon heterologous expression in yeast, tobacco BY2 cell and Arabidopsis seed. In cotton GhCPS1 and 2 gene expression correlates with the total CFA content in roots, stems and seeds. That GhCPS1 and 2 are expressed at a similar level in seed suggests both of them can be considered potential targets for gene silencing to reduce undesirable seed CPE accumulation. Because GhCPS1 is more active in yeast than the published Sterculia CPS and shows similar activity when expressed in model plant systems, it represents a strong candidate gene for

Background Cyclopropane fattyacids (CPA) have been found in certain gymnosperms, Malvales, Litchi and other Sapindales. The presence of their unique strained ring structures confers physical and chemical properties characteristic of unsaturated fattyacids with the oxidative stability displayed by saturated fattyacids making them of considerable industrial interest. While cyclopropenoid fattyacids (CPE) are well-known inhibitors of fattyacid desaturation in animals, CPE can also inhibit the stearoyl-CoA desaturase and interfere with the maturation and reproduction of some insect species suggesting that in addition to their traditional role as storage lipids, CPE can contribute to the protection of plants from herbivory. Results Three genes encoding cyclopropane synthase homologues GhCPS1, GhCPS2 and GhCPS3 were identified in cotton. Determination of gene transcript abundance revealed differences among the expression of GhCPS1, 2 and 3 showing high, intermediate and low levels, respectively, of transcripts in roots and stems; whereas GhCPS1 and 2 are both expressed at low levels in seeds. Analyses of fattyacid composition in different tissues indicate that the expression patterns of GhCPS1 and 2 correlate with cyclic fattyacid (CFA) distribution. Deletion of the N-terminal oxidase domain lowered GhCPS's ability to produce cyclopropane fattyacid by approximately 70%. GhCPS1 and 2, but not 3 resulted in the production of cyclopropane fattyacids upon heterologous expression in yeast, tobacco BY2 cell and Arabidopsis seed. Conclusions In cotton GhCPS1 and 2 gene expression correlates with the total CFA content in roots, stems and seeds. That GhCPS1 and 2 are expressed at a similar level in seed suggests both of them can be considered potential targets for gene silencing to reduce undesirable seed CPE accumulation. Because GhCPS1 is more active in yeast than the published Sterculia CPS and shows similar activity when expressed in model plant systems, it

Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti-inflammatory effects of n-3 fattyacids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fattyacid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fattyacids or their mediators; consequently supplementing with n-3 fattyacids is an attractive non-pharmacological intervention which may benefit asthma. PMID:26809946

Soybean oil is produced domestically in large supply, averaging over 20 billion pounds per year with an annual carryover of more than one billion pounds. It is important to find new uses for this surplus soybean oil. Hydroxyl fattyacids and hydroxyl oils are platform materials for specialty chemi...

Purpose of review. This review focuses on the effect(s) of n-3 polyunsaturated fattyacids (PUFA) on gene transcription as determined from data generated using cDNA microarrays. Introduced within the past decade, this methodology allows detection of the expression of thousands of genes simultaneo...

The objective of this study was to compare the fattyacid (FA) composition of the intramuscular (i.m. fat of the longissimus muscle (LM) from three divergent breeds of cattle: Angus (AN, n=9), Brahman (BR, n=7), and Romosinuano (RM, n=11). Cattle were blocked by breed and finished within an average ...

Dietary lipids are an important source of highly digestible energy and are the only source of essential fattyacids required for normal growth and development. They are also carriers and assist in the absorption of fat-soluble nutrients, such as sterols and fat-soluble vitamins, serve as a source of...

Tilapia have been shown to have a dietary requirement for linoleic (n-6) series fattyacids (18:2n-6 or 20:4n-6). The optimum dietary levels of n-6 reported were 0.5 and 1% for redbelly tilapia (Tilapia zillii) and Nile tilapia (Oreochromis niloticus), respectively. Tilapia have been suggested to al...

We evaluated the effects of rearing temperature on the composition of fattyacids and stearoyl-CoA desaturase (SCD) activity and gene expression in GIFT (genetically improved farmed tilapia) tilapia. Three triplicate groups of fish were reared for 40 days at 22, 28, or 34 °C. At the end of the trial, the final body weight of juveniles reared at 28 °C was higher than that of fish reared at 22 or 34 °C. Feed intake, feed efficiency, and the protein efficiency ratio were also higher at 28 °C. The fattyacid composition of muscle tissue differed significantly (P activity of the SCD gene. Increased SCD activity and gene expression can increase the biosynthesis of MUFAs in GIFT tilapia muscle. Additionally, cold acclimation can decrease the content of TC and TG in GIFT tilapia, which can help increase cold tolerance. PMID:25939714

Highlights: •The function of the mitochondria fattyacid synthesis pathway is partially unknown. •Overexpression of the pathway causes transcriptional activation through PPARs. •Knock down of the pathway attenuates that activation. •The last enzyme in the pathway regulates its own transcription. •Products of the mtFASII pathway are able to drive nuclear transcription. -- Abstract: Mammalian cells contain two fattyacid synthesis pathways, the cytosolic FASI pathway, and the mitochondrial FASII pathway. The selection behind the conservation of the mitochondrial pathway is not completely understood, given the presence of the cytosolic FAS pathway. In this study, we show through heterologous gene reporter systems and PCR-based arrays that overexpression of MECR, the last step in the mtFASII pathway, causes modulation of gene expression through the PPAR pathway. Electromobility shift assays (EMSAs) demonstrate that overexpression of MECR causes increased binding of PPARs to DNA, while cell fractionation and imaging studies show that MECR remains localized to the mitochondria. Interestingly, knock down of the mtFASII pathway lessens the effect of MECR on this transcriptional modulation. Our data are most consistent with MECR-mediated transcriptional activation through products of the mtFASII pathway, although we cannot rule out MECR acting as a coactivator. Further investigation into the physiological relevance of this communication will be necessary to better understand some of the phenotypic consequences of deficits in this pathway observed in animal models and human disease.

Methods are provided for refining natural oil feedstocks and producing isomerized esters and acids. The methods comprise providing a C4-C18 unsaturated fatty ester or acid, and isomerizing the fattyacid ester or acid in the presence of heat or an isomerization catalyst to form an isomerized fatty ester or acid. In some embodiments, the methods comprise forming a dibasic ester or dibasic acid prior to the isomerizing step. In certain embodiments, the methods further comprise hydrolyzing the dibasic ester to form a dibasic acid. In certain embodiments, the olefin is formed by reacting the feedstock in the presence of a metathesis catalyst under conditions sufficient to form a metathesized product comprising olefins and esters, separating the olefins from the esters in the metathesized product, and transesterifying the esters in the presence of an alcohol to form a transesterified product having unsaturated esters.

FAT/CD36 is a membrane scavenger receptor that facilitates long chain fattyacid uptake by muscle. Acute increases in membrane CD36 and fattyacid uptake have been reported in response to insulin and contraction. In this study we have explored protein ubiquitination as one potential mechanism for the regulation of CD36 level. CD36 expressed in Chinese hamster ovary (CHO) or HEK 293 cells was found to be polyubiquitinated via a process involving both lysines 48 and 63 of ubiquitin. Using CHO cells expressing the insulin receptor (CHO/hIR) and CD36, it is shown that addition of insulin (100 nm, 10 and 30 min) significantly reduced CD36 ubiquitination. In contrast, ubiquitination was strongly enhanced by fattyacids (200 microm palmitate or oleate, 2 h). Similarly, endogenous CD36 in C2C12 myotubes was ubiquitinated, and this was enhanced by oleic acid treatment, which also reduced total CD36 protein in cell lysates. Insulin reduced CD36 ubiquitination, increased CD36 protein, and inhibited the opposite effects of fattyacids on both parameters. These changes were paralleled by changes in fattyacid uptake, which could be blocked by the CD36 inhibitor sulfosuccinimidyl oleate. Mutation of the two lysine residues in the carboxyl-terminal tail of CD36 markedly attenuated ubiquitination of the protein expressed in CHO cells and was associated with increased CD36 level and enhanced oleate uptake and incorporation into triglycerides. In conclusion, fattyacids and insulin induce opposite alterations in CD36 ubiquitination, modulating CD36 level and fattyacid uptake. Altered CD36 turnover may contribute to abnormal fattyacid uptake in the insulin-resistant muscle. PMID:18353783

Here, we assessed the effects of long-chain fattyacids (LCFAs) and the LCFA receptor agonist GW9508 on the transcription of the gonadotropin subunit genes Cga, Lhb and Fshb because LCFA receptor GPR120 was observed in mouse gonadotropes in our recent study. A transcription assay using LβT2 cells demonstrated that LCFAs, oleic acid, α-linolenic acid, docosahexaenoic acid and palmitate, repressed the expression of Cga, Lhb, and Fshb at concentrations between 50 and 100 µM. On the other hand, treatment with 10 µM unsaturated LCFAs, oleic acid, α-linolenic acid and docosahexaenoic acid, repressed only Fshb expression, while the same dose of a saturated LCFA, palmitate, had no effect on the expression of gonadotropin subunit genes. Furthermore, GW9508 did not affect promoter activity. Next, we examined deletion mutants of the upstream region of Fshb and found that the upstream regulatory region (-2824 to -2343 bp) of Fshb was responsible for the notable repression by 10 µM unsaturated LCFAs. Our results suggest that the upstream region of Fshb is susceptible to unsaturated LCFAs. In addition, unsaturated LCFAs play a role in repressing Fshb expression through the distal -2824 to -2343 bp region, which might be independent of the LCFA receptor GPR120 pathway. PMID:26853521

Peroxisome proliferator activated receptors beta1 (PPARβ1) and beta2 (PPARβ2) were investigated in loach (Misgurnus anguillicaudatus). The PPARβ1 and PPARβ2 were widely distributed in loach tissues. Multiple alignments of deduced amino acid sequences revealed homologous characteristics of the two subtypes of PPARβ with 88% identity. PPARβ1 was markedly expressed in the liver, about 100-fold higher than liver PPARβ2. The two subtypes in unfertilized ovum (UO) showed the highest transcriptions in early life stages, and there were great divergences in expression between unfertilized and fertilized stages. The regulation of PPARβ1 and PPARβ2 in response to dietary fattyacids was studied in liver of loach fed with diets containing fish oil (FO, rich in n-3 highly unsaturated fattyacid) or soybean oil (SO, rich in 18:2n-6) for 75days. Results showed that hepatic transcription of PPARβ1 in the SO group was higher than in the FO group. However, PPARβ2 expression was similar. The differences of molecular characterization, tissue expressions in early life stages, and transcriptional regulation by lipid resources indicated that PPARβ1 and PPARβ2 were functionally different. This is the first report of differential expression of PPARβ1 and PPARβ2 in various tissues and early life stages of loach are regulated by lipid resources. These results will stimulate further studies to better understand the functional characterization of PPARβ1 and PPARβ2. PMID:26654955

The phospholipids and fattyacids of two strains of Neisseria gonorrhoeae of different penicillin susceptibilities were examined. The phospholipids, which comprise about 8% of the dry weight of the cells, consisted of phosphatidylethanolamine (70%) and phosphatidylglycerol (20%); small amounts of phosphatidylcholine and traces of cardiolipin were also present. Growing and stationary-phase cells were similar in content and composition of phospholipids except for phosphatidylcholine, which increased two- to fivefold in the stationary-phase cells. The fattyacids of the phospholipids were characterized by two major acids, palmitic and a C16:1, with myristic and a C18:1 acid present in smaller amounts. The fattyacids present in purified phospholipid fractions varied considerably in relative proportions from fraction to fraction. No significant difference in the composition of phospholipids from the two strains was evident. Large amounts of beta-hydroxy lauric acid were detected only after saponification of the organisms. Differences in the lipid composition between the gonococcus and other gram-negative bacteria are discussed. PMID:810478

The reported effects of different families of fattyacids (FA; SFA, MUFA, n-3 and n-6 PUFA) on human health and the importance of macrophage respiratory burst and cytokine release to immune defence led us to examine the influence of palmitic acid (PA), oleic acid (OA), linoleic acid, arachidonic acid, EPA and DHA on macrophage function. We determined fungicidal activity, reactive oxygen species (ROS) and cytokine production after the treatment of J774 cells with non-toxic concentrations of the FA. PA had a late and discrete stimulating effect on ROS production, which may be associated with the reduced fungicidal activity of the cells after treatment with this FA. OA presented a sustained stimulatory effect on ROS production and increased fungicidal activity of the cells, suggesting that enrichment of diets with OA may be beneficial for pathogen elimination. The effects of PUFA on ROS production were time- and dose-dependently regulated, with no evident differences between n-3 and n-6 PUFA. It was worth noting that most changes induced after stimulation of the cells with lipopolysaccharide were suppressed by the FA. The present results suggest that supplementation of the diet with specific FA, not classes of FA, might enable an improvement in host defence mechanisms or a reduction in adverse immunological reactions. PMID:21232170

Oxygenated fattyacids were identified in oat grain by gas chromatography - mass spectrometry. We hypothesized that most of these were the results of lipoxygenase activity. This hypothesis was tested by measuring concentrations of these compounds after hydrothermal treatments and storage of oat groa...

In Western countries the dietary guidance emphasizes the need to decrease the intake of saturated fattyacids and to replace them with polyunsaturated fattyacids (PUFA), particularly long chain n-3 PUFA (LC-PUFA). The production of poultry meat having a lower fat content and healthier fattyacid (FA) profile is a hot topic for the poultry industry, and the possibility to identify genotypes able to produce meat with a higher LC-PUFA content deserves attention. The aims of the present study were to evidence in chicken (i) a genotype-related different expression of the desaturating enzymes delta-6 (Δ6, EC 1.14.99.25), delta-5 (Δ5, EC 1.14.19.) and delta-9 (Δ9, EC 1.14.19.1); (ii) the impact of the hypothesized different expression on the meat FA composition; (iii) the distribution of desaturase products in the different lipid classes. Slow (SG), medium (MG) and fast (FG) growing chickens fed the same diet were evaluated either for the relative expression of FADS1, FADS2 and SCD1 genes in liver (by q-PCR), or for the FA composition of breast meat. MG and particularly SG birds showed a greater expression of FADS2 and FADS1 genes, a higher Δ6 and Δ5 activity (estimated using desaturase indices), and consequently a higher LC-PUFA content in the breast meat than FG birds. The relationship between genotype and desaturating ability was demonstrated, with a significant impact on the PUFA content of breast meat. Due to the high consumption rate of avian meat, the identification of the best genotypes for meat production could represent an important goal not only for the food industry, but also for the improvement of human nutrition. PMID:26670346

In marine bacteria and some thraustochytrids (marine stramenopiles) long-chain polyunsaturated fattyacids (LC-PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are produced de novo by PUFA synthases. These large, multi-domain enzymes carry out the multitude of individual reactions required for conversion of malonyl-CoA to the final LC-PUFA products. Here we report on the release of fattyacids from the PUFA synthase found in Schizochytrium, a thraustochytrid that has been developed as a commercial source for DHA-enriched biomass and oil. Data from in vitro activity assays indicate that the PUFAs are released from the enzyme as free fattyacids (FFAs). Addition of ATP and Mg(2+) to in vitro assays facilitates appearance of radiolabel from (14)C-malonyl-CoA in a triacylglycerol fraction, suggesting the involvement of acyl-CoA synthetases (ACS). Furthermore, addition of triascin C, an inhibitor of ACSs, to the assays blocks this conversion. When the Schizochytrium PUFA synthase is expressed in Escherichia coli, the products of the enzyme accumulate as FFAs, suggesting that the thioesterase activity required for fattyacid release is an integral part of the PUFA synthase. PMID:19272783

Oxygenated (hydroxy-, epoxy-) fattyacids such as ricinoleic, vernolic and /or sebacic acids are high value chemicals and can be used to produce polymers and specialty chemicals. Oxygenated fattyacids also have many bioactive properties, such as antimicrobial activity against Salmonella, Staphyloc...

This review deals with the recent findings on the microbial conversion of essential fattyacids (EFAs) through Pseudomonas aeruginosa PR3 NRRL-B-18602, and the antimicrobial properties of bioconverted essential fattyacids, with particular emphasis on n-3 or n-6 fattyacids. The first section deals...

... Multipurpose Additives § 172.863 Salts of fattyacids. The food additive salts of fattyacids may be safely... conditions: (a) The additive consists of one or any mixture of two or more of the aluminum, calcium... derived from tall oil fattyacids conforming with § 172.862. (b) The food additive is used or intended...

Natural occurring fattyacids are a large and complex class of compounds found in plants and animals. Fattyacids are abundant and of interest because of their renewability, biodegradability, biocompatibility, low cost, and fascinating chemistry. Of the many fattyacids, only 20-25 of them are widel...

The present invention relates to methods for producing fattyacid desaturase mutants having a substantially increased activity towards substrates with fewer than 18 carbon atom chains relative to an unmutagenized precursor desaturase having an 18 carbon chain length specificity, the sequences encoding the desaturases and to the desaturases that are produced by the methods. The present invention further relates to a method for altering a function of a protein, including a fattyacid desaturase, through directed mutagenesis involving identifying candidate amino acid residues, producing a library of mutants of the protein by simultaneously randomizing all amino acid candidates, and selecting for mutants which exhibit the desired alteration of function. Candidate amino acids are identified by a combination of methods. Enzymatic, binding, structural and other functions of proteins can be altered by the method.

The effect of dissolution from particulates into the supernatant solution in sediment trap sample cups has been measured for fattyacids. A mooring array with time series sediment traps was deployed in the northeast Atlantic Ocean (59°N, 21°W) for 14 months. Selected representative samples from the trap at 2200 m (poisoned with NaN3) were analyzed for total and free fattyacids in both the solution and particulate phase by means of gas chromatography-mass spectrometry with an ion trap detector. The flux contribution of the dissolved total fattyacids (∑ DTFA) was found to be between 15 and 75% of the total flux (∑ TTFA, sum of the fluxes of total fattyacids in both particles and supernatants). Dissolved free fattyacids (∑ DFFA) represented 25-88% of the total flux of free fattyacids (∑ TFFA). Absolute concentrations of total and free fattyacids in both compartments are discussed in terms of the processes controlling the distribution between the two phases, for example, readsorption. Sample handling, poisoning, bacterial activity, and swimmers may also affect fattyacid distribution. Flux data (sum of particulate and dissolved fluxes) are presented for individual fattyacids. Also, the degree of dissolution of individual fattyacids is shown for one sample (dissolved fraction ranging between 16 and 98% of total flux).

Fattyacid amino acid conjugates (FACs) have been found in Noctuid as well as Sphingid caterpillar oral secretions and especially volicitin [N-(17-hydroxylinolenoyl)-L-Glutamine] and its biochemical precursor, N-linolenoyl-L-glutamine, are known elicitors of induced volatile emissions in corn plants...

The phospholipid fattyacid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fattyacids and a higher unsaturation index and polyunsaturated fattyacids/saturated fattyacids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fattyacids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogernic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats.

Ammonolysis of fattyacids to the corresponding fattyacid amides is efficiently catalysed by Candida antartica lipase (Novozym 435). In the present paper lipase-catalysed synthesis of erucamide by ammonolysis of erucic acid and urea in organic solvent medium was studied and optimal conditions for fatty amides synthesis were established. In this process erucic acid gave 88.74 % pure erucamide after 48 hour and 250 rpm at 60 degrees C with 1:4 molar ratio of erucic acid and urea, the organic solvent media is 50 ml tert-butyl alcohol (2-methyl-2-propanol). This process for synthesis is economical as we used urea in place of ammonia or other amidation reactant at atmospheric pressure. The amount of catalyst used is 3 %. PMID:17898456

The optimal conditions of supercritical carbon dioxide (SC-CO2) (160-220 bars, 40-80 °C) technology combined with co-solvent (ethanol), to recover oil, flavonolignans (silychristin, silydianin and silybinin) and fattyacids from milk thistle seeds, to be used as food additives and/or nutraceuticals, were studied. Moreover, the antioxidant and cytotoxic activities of the SC-CO2 oil seeds extracts were evaluated in Caco-2 carcinoma cells. Pressure and temperature had a significant effect on oil and flavonolignans recovery, although there was not observed a clear trend. SC-CO2 with co-solvent extraction at 220 bars, 40 °C was the optimum treatment to recover oil (30.8%) and flavonolignans from milk thistle seeds. Moreover, linoleic (47.64-66.70%), and oleic (19.68-24.83%) acids were the predominant fattyacids in the oil extracts recovered from milk thistle under SC-CO2. In addition, SC-CO2 extract showed a high antioxidant activity determined by DPPH and ABTS tests. Cytotoxic activities of silychristin, silydianin and silybinin and the obtained SC-CO2 extract (220 bars, 40 °C) were evaluated against Caco-2 cells. The SC-CO2 extract inhibited the proliferation of Caco-2 cells in a dose-responsive manner and induced the highest percentage of mortality of Caco-2 cells (from 43 to 71% for concentrations from 10 up to 100 μg/ml of SC-CO2 oil seeds). PMID:26172510

Reconstitution of nonnative, very-long-chain polyunsaturated fattyacid (VLC-PUFA) biosynthetic pathways in Arabidopsis thaliana was undertaken. The introduction of three primary biosynthetic activities to cells requires the stable coexpression of multiple proteins within the same cell. Herein, we report that C22 VLC-PUFAs were synthesized from C18 precursors by reactions catalyzed by Δ6-desaturase, an ELOVL5-like enzyme involved in VLC-PUFA elongation, and Δ5-desaturase. Coexpression of the corresponding genes (McD6DES, AsELOVL5, and PtD5DES) under the control of the seed-specific vicilin promoter resulted in production of docosapentaenoic acid (22:5 n-3) and docosatetraenoic acid (22:4 n-6) as well as eicosapentaenoic acid (20:5 n-3) and arachidonic acid (20:4 n-6) in Arabidopsis seeds. The contributions of the transgenic enzymes and endogenous fattyacid metabolism were determined. Specifically, the reasonable synthesis of omega-3 stearidonic acid (18:4 n-3) could be a useful tool to obtain a sustainable system for the production of omega-3 fattyacids in seeds of a transgenic T3 line 63-1. The results indicated that coexpression of the three proteins was stable. Therefore, this study suggests that metabolic engineering of oilseed crops to produce VLC-PUFAs is feasible. PMID:26339641

Supported metal catalysts containing 5 wt% Pd on silica, alumina, and activated carbon were evaluated for liquid-phase deoxygenation of stearic (octadecanoic), lauric (dodecanoic), and capric (decanoic) acids under 5 % H-2 at 300 A degrees C and 15 atm. On-line quadrupole mass spectrometry (QMS) was used to measure CO + CO2 yield, CO2 selectivity, H-2 consumption, and initial decarboxylation rate. Post-reaction analysis of liquid products by gas chromatography was used to determine n-alkane yields. The Pd/C catalyst was highly active and selective for stearic acid (SA) decarboxylation under these conditions. In contrast, SA deoxygenation over Pd/SiO2 occurred primarily via decarbonylation and at a much slower rate. Pd/Al2O3 exhibited high initial SA decarboxylation activity but deactivated under the test conditions. Similar CO2 selectivity patterns among the catalysts were observed for deoxygenation of lauric and capric acids; however, the initial decarboxylation rates tended to be lower for these substrates. The influence of alkyl chain length on deoxygenation kinetics was investigated for a homologous series of C-10-C-18 fattyacids using the Pd/C catalyst. As fattyacid carbon number decreases, reaction time and H-2 consumption increase, and CO2 selectivity and initial decarboxylation rate decrease. The increase in initial decarboxylation rates for longer chain fattyacids is attributed to their greater propensity for adsorption on the activated carbon support.

Cachexia is a devastating muscle-wasting syndrome that occurs in patients who have chronic diseases. It is most commonly observed in individuals with advanced cancer, presenting in 80% of these patients, and it is one of the primary causes of morbidity and mortality associated with cancer. Additionally, although many people with cachexia show hypermetabolism, the causative role of metabolism in muscle atrophy has been unclear. To understand the molecular basis of cachexia-associated muscle atrophy, it is necessary to develop accurate models of the condition. By using transcriptomics and cytokine profiling of human muscle stem cell-based models and human cancer-induced cachexia models in mice, we found that cachectic cancer cells secreted many inflammatory factors that rapidly led to high levels of fattyacid metabolism and to the activation of a p38 stress-response signature in skeletal muscles, before manifestation of cachectic muscle atrophy occurred. Metabolomics profiling revealed that factors secreted by cachectic cancer cells rapidly induce excessive fattyacid oxidation in human myotubes, which leads to oxidative stress, p38 activation and impaired muscle growth. Pharmacological blockade of fattyacid oxidation not only rescued human myotubes, but also improved muscle mass and body weight in cancer cachexia models in vivo. Therefore, fattyacid-induced oxidative stress could be targeted to prevent cancer-induced cachexia. PMID:27135739

Fattyacids are the primary fuel for the heart and are ligands for peroxisome proliferator-activated receptors (PPARs), which regulate the expression of genes encoding proteins involved in fattyacid metabolism. Saturated fattyacids, particularly palmitate, can be converted to the proapoptotic lipi...

Modulation of fat metabolism is an important component of the etiology of obesity as well as individual response to weight loss program. The influence of lipolysis process had receives many attentions in recent decades. Compared to that, fattyacid oxidation which occurred after lipolysis seems to be less exposed. There are limited publications on how fattyacid oxidation influences predisposition to obesity, especially the importance of genetic variations of fattyacid oxidation proteins on development of obesity. The aim of this review is to provide recent knowledge on how polymorphism of genes related fattyacid oxidation is obtained. Studies in human as well as animal model showed that disturbance of genes related fattyacid oxidation process gave impact on body weight and risks to obesity. Several polymorphisms on CD36, CPT, ACS and FABP had been shown to be related to obesity either by regulating enzymatic activity or directly influence fattyacid oxidation process. PMID:27127449

In order to determine whether placental cells can synthesize and release fattyacids, trophoblast cells from term human placentas were established in monolayer culture. The cells continued to secrete placental lactogen and progesterone and maintained specific activities of critical enzymes of triacylglycerol and phosphatidylcholine biosynthesis for 24 to 72 hr in culture. Fattyacid was rapidly synthesized from (/sup 14/C)acetate and released by the cells. Palmitoleic, palmitic, and oleic acids were the major fattyacids synthesized from (/sup 14/C)acetate and released. Small amounts of lauric, myristic, and stearic acids were also identified. (/sup 14/C)acetate was also incorporated into cellular triacylglycerol, phospholipid, and cholesterol, but radiolabeled free fattyacid did not accumulate intracellularly. In a pulse-chase experiment, cellular glycerolipids were labeled with (1-/sup 14/C)oleate; trophoblast cells then released /sup 14/C-labeled fattyacid into the media as the cellular content of labeled phospholipid and triacylglycerol decreased without intracellular accumulation of free fattyacid. Twenty percent of the /sup 14/C-label lost from cellular glycerolipid could not be recovered as a chloroform-extractable product, suggesting that some of the hydrolyzed fattyacid had been oxidized. These data indicate that cultured placenta trophoblast cells can release fattyacids that have either been synthesized de novo or that have been hydrolyzed from cellular glycerolipids. Trophoblast cells in monolayer culture should provide an excellent model for molecular studies of placental fattyacid metabolism and release.

Myocardial fuel selection is a key feature of the health and function of the heart, with clear links between myocardial function and fuel selection and important impacts of fuel selection on ischemia tolerance. Radiopharmaceuticals provide uniquely valuable tools for in vivo, non-invasive assessment of these aspects of cardiac function and metabolism. Here we review the landscape of imaging probes developed to provide non-invasive assessment of myocardial fattyacid oxidation (MFAO). Also, we review the state of current knowledge that myocardial fattyacid imaging has helped establish of static and dynamic fuel selection that characterizes cardiac and cardiometabolic disease and the interplay between fuel selection and various aspects of cardiac function. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26923433

In the representative gut bacterium Lactobacillus plantarum, we identified genes encoding the enzymes involved in a saturation metabolism of polyunsaturated fattyacids and revealed in detail the metabolic pathway that generates hydroxy fattyacids, oxo fattyacids, conjugated fattyacids, and partially saturated trans-fattyacids as intermediates. Furthermore, we observed these intermediates, especially hydroxy fattyacids, in host organs. Levels of hydroxy fattyacids were much higher in specific pathogen-free mice than in germ-free mice, indicating that these fattyacids are generated through polyunsaturated fattyacids metabolism of gastrointestinal microorganisms. These findings suggested that lipid metabolism by gastrointestinal microbes affects the health of the host by modifying fattyacid composition. PMID:24127592

The free fattyacid receptor 1 (FFA1) has attracted extensive attention as a novel antidiabetic target in the last decade. Several FFA1 agonists reported in the literature have been suffered from relatively high molecular weight and lipophilicity. We have previously reported the FFA1 agonist 1. Based on the common amide structural characteristic of SAR1 and NIH screened compound, we here describe the continued structure-activity exploration to decrease the molecular weight and lipophilicity of the compound 1 series by converting various amide linkers. All of these efforts lead to the discovery of the preferable lead compound 18, a compound with considerable agonistic activity, high LE and LLE values, lower lipophilicity than previously reported agonists, and appreciable efficacy on glucose tolerance in both normal and type 2 diabetic mice. PMID:26420383

The n-3 polyunsaturated fattyacids (PUFA) appear to have antiinflammatory properties that can be partly explained by their biological activity on leukocytes. Since leukocyte emigration is an essential component of the inflammatory response, we have examined the effects of the n-3 PUFA (eicosapentaenoic and docosahexaenoic acids) on neutrophil random and chemotactic movement. Preexposure of neutrophils for 15-30 min to 1-10 micrograms/ml PUFA reduced the random and chemotactic migration to both FMLP- and fungi-activated complement. The inhibitory effect diminished with increasing saturation and carbon chain length, and methylation abolished this activity. Arachidonic and docosahexaenoic acids were the most activefattyacids. The PUFA concentration required to inhibit migration was dependent on cell number, suggesting that the fattyacid effects on leukocyte migration in vivo may be governed by the stage of the inflammatory response. It was concluded that the PUFA rather than their metabolites were responsible for the inhibition since: (a) antioxidants did not prevent the PUFA-induced migration inhibition and the hydroxylated intermediates were less active, and (b) inhibitors of the cyclooxygenase and lipoxygenase pathways were without effect. Inhibitors of protein kinases and calmodulin-dependent enzyme system did not prevent the PUFA-induced migration inhibition, which was also independent of phospholipase D-catalyzed hydrolysis of phospholipids. It is also shown that PUFA decrease the FMLP-induced Ca2+ mobilization. Images PMID:8132744

Excess energy is stored primarily as triglycerides, which are mobilized when demand for energy arises. Dysfunction of energy balance by excess food intake leads to metabolic diseases, such as obesity and diabetes. Free fattyacids (FFAs) provided by dietary fat are not only important nutrients, but also contribute key physiological functions via FFA receptor (FFAR)-mediated signaling molecules, which depend on FFAs' carbon chain length and the ligand specificity of the receptors. Functional analyses have revealed that FFARs are critical for metabolic functions, such as peptide hormone secretion and inflammation, and contribute to energy homeostasis. In particular, recent studies have shown that the administration of selective agonists of G protein-coupled receptor (GPR) 40 and GPR120 improved glucose metabolism and systemic metabolic disorders. Furthermore, the anti-inflammation and energy metabolism effects of short chain FAs have been linked to the activation of GPR41 and GPR43. In this review, we summarize recent progress in research on FFAs and their physiological roles in the regulation of energy metabolism. PMID:27023530

Excess energy is stored primarily as triglycerides, which are mobilized when demand for energy arises. Dysfunction of energy balance by excess food intake leads to metabolic diseases, such as obesity and diabetes. Free fattyacids (FFAs) provided by dietary fat are not only important nutrients, but also contribute key physiological functions via FFA receptor (FFAR)-mediated signaling molecules, which depend on FFAs’ carbon chain length and the ligand specificity of the receptors. Functional analyses have revealed that FFARs are critical for metabolic functions, such as peptide hormone secretion and inflammation, and contribute to energy homeostasis. In particular, recent studies have shown that the administration of selective agonists of G protein-coupled receptor (GPR) 40 and GPR120 improved glucose metabolism and systemic metabolic disorders. Furthermore, the anti-inflammation and energy metabolism effects of short chain FAs have been linked to the activation of GPR41 and GPR43. In this review, we summarize recent progress in research on FFAs and their physiological roles in the regulation of energy metabolism. PMID:27023530

The cellular fattyacid composition of eight Haemophilus equigenitalis strains was determined by gas-liquid chromatography. All strains showed a grossly similar pattern characterized by large amounts of 18:1 and 16:0. The amounts of 16:1, 18:2, 18:0, 3-OH 14:0, 3-OH 16:0, and 3-OH 18:1 were relatively small. PMID:7096556

Anorexia nervosa is a serious neurobehavioral disorder marked by semistarvation, extreme fear of weight gain, frequently hyperactivity, and low body temperature. The etiology remains unknown. We present a speculation that a primary causative factor is that polyunsaturated fattyacids are skewed to prevent oxidative damage in phospholipid membranes. This causes a change in the trade off of oxidation protection vs homeoviscous adaptation to lower temperatures, which sets off a metabolic cascade that leads to the rogue state of anorexia nervosa. PMID:25981875

Ricinoleic acid (12-hydroxyoctadec-cis-9-enoic acid) has many specialized uses in bioproduct industries, while castor bean is currently the only commercial source for the fattyacid. This report describes metabolic engineering of a microbial system (Pichia pastoris) to produce ricinoleic acid using a "push" (synthesis) and "pull" (assembly) strategy. CpFAH, a fattyacid hydroxylase from Claviceps purpurea, was used for synthesis of ricinoleic acid, and CpDGAT1, a diacylglycerol acyl transferase for the triacylglycerol synthesis from the same species, was used for assembly of the fattyacid. Coexpression of CpFAH and CpDGAT1 produced higher lipid contents and ricinoleic acid levels than expression of CpFAH alone. Coexpression in a mutant haploid strain defective in the Δ12 desaturase activity resulted in a higher level of ricinoleic acid than that in the diploid strain. Intriguingly, the ricinoleic acid produced was mainly distributed in the neutral lipid fractions, particularly the free fattyacid form, but with little in the polar lipids. This work demonstrates the effectiveness of the metabolic engineering strategy and excellent capacity of the microbial system for production of ricinoleic acid as an alternative to plant sources for industrial uses. PMID:26323290

The fattyacid profile of hepatocytes and adipocytes is determined by the composition of the dietary lipids. It remains unclear which fattyacid components contribute to the development or reduction of insulin resistance. The present work examined the fattyacid composition of both tissues in sucrose-induced obese rats receiving fish oil to determine whether the effect of dietary (n-3) polyunsaturated fattyacids (PUFAs) on the reversion of metabolic syndrome in these rats is associated to changes in the fattyacid composition of hepatocyte and adipocyte membrane lipids. Animals with metabolic syndrome were divided into a corn-canola oil diet group and a fish oil diet group, and tissues fattyacids composition were analyzed after 6 weeks of dietary treatment. Fattyacid profiles of the total membrane lipids were modified by the fattyacid composition of the diets fed to rats. N-3 PUFAs levels in animals receiving the fish oil diet plus sucrose in drinking water were significantly higher than in animals under corn-canola oil diets. It is concluded that in sucrose-induced obese rats, consumption of dietary fish oil had beneficial effects on the metabolic syndrome and that such effects would be conditioned by the changes in the n-3 PUFAs composition in hepatic and adipose tissues because they alter membrane properties and modify the type of substrates available for the production of active lipid metabolites acting on insulin resistance and obesity. PMID:21695545

Lipid mediators are produced from the oxidation of polyunsaturated fattyacids through enzymatic and free radical-mediated reactions. When subject to oxygenation via cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases, polyunsaturated fattyacids give rise to an array of metabolites including eicosanoids, docosanoids, and octadecanoids. These potent bioactive lipids are involved in many biochemical and signaling pathways, with inflammation being of particular importance. Moreover, because they are produced by more than one pathway and substrate, and are present in a variety of biological milieus, their analysis is not always possible with conventional assays. Liquid chromatography coupled to electrospray mass spectrometry offers a versatile and sensitive approach for the analysis of bioactive lipids, allowing specific and accurate quantitation of multiple species present in the same sample. Here we explain the principles of this approach to mediator lipidomics and present detailed protocols for the assay of enzymatically produced oxygenated metabolites of polyunsaturated fattyacids that can be tailored to answer biological questions or facilitate assessment of nutritional and pharmacological interventions. PMID:22940496

The endogenous production of long-chain polyunsaturated fattyacids (LC-PUFA) in carnivorous teleost species inhabiting freshwater environments is poorly understood. Although a predatory lifestyle could potentially supply sufficient LC-PUFA to satisfy the requirements of these species, the nutrient-poor characteristics of the freshwater food web could impede this advantage. In this study, we report the cloning and functional characterisation of an elongase enzyme in the LC-PUFA biosynthesis pathway from striped snakehead (Channa striata), which is a strict freshwater piscivore that shows high deposition of LC-PUFA in its flesh. We also functionally characterised a previously isolated fatty acyl desaturase cDNA from this species. Results showed that the striped snakehead desaturase is capable of Δ4 and Δ5 desaturation activities, while the elongase showed the characteristics of Elovl5 elongases. Collectively, these findings reveal that striped snakehead exhibits the genetic resources to synthesise docosahexaenoic acid (DHA; 22:6n-3) from eicosapentaenoic acid (EPA; 20:5n-3). Both genes are expressed at considerable levels in the brain and the liver. In liver, both genes were up-regulated by dietary C18 PUFA, although this increase did not correspond to a significant rise in the deposition of muscle LC-PUFA. Brain tissue of fish fed with plant oil diets showed higher expression of fads2 gene compared to fish fed with fish oil-based diet, which could ensure DHA levels remain constant under limited dietary DHA intake. This suggests the importance of DHA production from EPA via the ∆4 desaturation step in order to maintain an optimal reserve of DHA in the neuronal tissues of carnivores. PMID:25542509

Thespesia populnea belongs to the plant family of Malvaceae which contain cyclopropane and cyclopropene fattyacids. However, previous literature reports vary regarding the content of these compounds in Thespesia populnea seed oil. In this work, the content of malvalic acid (8,9-methylene-9-heptade...

The fattyacid profiles of six seed oils of the Fabaceae (Leguminosae) family are reported and discussed. These are the seed oils of Centrosema pubescens, Clitoria ternatea, Crotalaria mucronata, Macroptilium lathyroides, Pachyrhizus erosus, and Senna alata. The most common fattyacid in the fatty a...

This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fattyacids in transgenic plants.

Carnitine is essential for the transfer of long-chain fattyacids across the inner mitochondrial membrane for subsequent β-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B(0,+). Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients' fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler

Polyunsaturated fattyacids (PUFA) are oxidized by cytochrome P450 epoxygenases to PUFA epoxides which function as potent lipid mediators. The major metabolic pathways of PUFA epoxides are incorporation into phospholipids and hydrolysis to the corresponding PUFA diols by soluble epoxide hydrolase. Inhibitors of soluble epoxide hydrolase stabilize PUFA epoxides and potentiate their functional effects. The epoxyeicosatrienoic acids (EETs) synthesized from arachidonic acid produce vasodilation, stimulate angiogenesis, have anti-inflammatory actions, and protect the heart against ischemia-reperfusion injury. EETs produce these functional effects by activating receptor-mediated signaling pathways and ion channels. The epoxyeicosatetraenoic acids synthesized from eicosapentaenoic acid and epoxydocosapentaenoic acids synthesized from docosahexaenoic acid are potent inhibitors of cardiac arrhythmias. Epoxydocosapentaenoic acids also inhibit angiogenesis, decrease inflammatory and neuropathic pain, and reduce tumor metastasis. These findings indicate that a number of the beneficial functions of PUFA may be due to their conversion to PUFA epoxides. PMID:25093613

This experiment examined the time course over which the amount of dietary essential fattyacids (EFA) affects brain mitochondrial fattyacids. Weanling rats were fed 20% (wt/wt) fat diets that contained either 4 or 15% (wt/wt of diet) EFA for 1, 2, 3 or 6 wk or a 10% EFA diet for 3 or 6 wk. The EFA ratio [18:2(n-6)/18:3(n-3)] of all diets was approximately 30. Fattyacid analysis of brain mitochondrial phosphatidylethanolamine, phosphatidylcholine and cardiolipin revealed that the largest dietary effect was on 18:2(n-6), which was 30% higher in rats fed the 15 vs. 4% EFA diets after 1 wk. This difference increased to twofold by 3 wk and was still twofold after 6 wk. These results demonstrate several facts: 1) the response of 18:2(n-6) in cardiolipin to dietary EFA is very fast and large, relative to changes in other quantitatively major fattyacids observed in weanling rats; 2) the 18:2(n-6) level in neural cardiolipin stabilizes after 3 wk of feeding at a level dependent upon the amount of dietary EFA; and 3) at least one neural fattyacid, 18:2(n-6), is very sensitive to amounts of dietary EFA that are well above the animal's EFA requirement. PMID:1765818

According to report, temperature of growth of thermotolerant, methane-oxidizing bacterium Methylococcus capsulatus (Bath) affects both proportion of monounsaturated fattyacids and cis/trans ratio of these acids in cell membrane. Because suboptimum growth temperature is potential stress factor, it may be possible to use such cis/trans ratios as indices of stresses upon methane-oxidizing microbial communities. Research in microbiology of methanotrophs increasing because of possible commercial exploitation of these organisms as biocatalysts or as sources of useful polymers; knowledge of effect of temperature on ability of methanotrophs to utilize methane useful in optimization of conditions of growth.

Free fattyacids and monoglycerides have long been known to possess broad-spectrum antibacterial activity that is based on lytic behavior against bacterial cell membranes. Considering the growing challenges of drug-resistant bacteria and the need for new classes of antibiotics, the wide prevalence, affordable cost, and broad spectrum of fattyacids and monoglycerides make them attractive agents to develop for healthcare and biotechnology applications. The aim of this review is to provide a brief introduction to the history of antimicrobial lipids and their current status and challenges, and to present a detailed discussion of ongoing research efforts to develop nanotechnology formulations of fattyacids and monoglycerides that enable superior in vitro and in vivo performance. Examples of nano-emulsions, liposomes, solid lipid nanoparticles, and controlled release hydrogels are presented in order to highlight the potential that lies ahead for fattyacids and monoglycerides as next-generation antibacterial solutions. Possible application routes and future directions in research and development are also discussed. PMID:26950108

A high-fat diet and elevated levels of free fattyacids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fattyacids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fattyacids, including short-chain and certain unsaturated fattyacids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system. PMID:27006755

The effects of postharvest oxalic acid (OA) treatment on chilling injury, energy metabolism and membrane fattyacid content in 'Baifeng' peach fruit stored at 0°C were investigated. Internal browning was significantly reduced by OA treatment in peaches. OA treatment markedly inhibited the increase of ion leakage and the accumulation of malondialdehyde. Meanwhile, OA significantly increased the contents of adenosine triphosphate and energy charge in peach fruit. Enzyme activities of energy metabolism including H(+)-adenosine triphosphatase, Ca(2+)-adenosine triphosphatase, succinic dehydrogenase and cytochrome C oxidase were markedly enhanced by OA treatment. The ratio of unsaturated/saturated fattyacid in OA-treated fruit was significantly higher than that in control fruit. These results suggest that the alleviation in chilling injury by OA may be due to enhanced enzyme activities related to energy metabolism and higher levels of energy status and unsaturated/saturated fattyacid ratio. PMID:24837925

The biosynthesis of platelet-activating factor (PAF), a phospholipid autocoid with potent ulcerogenic properties that is produced in secretory exocrine glands by physiological secretagogues, was assessed in microsomal preparations of glandular gastric mucosa. For this purpose, 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PAF):acetyl-CoA acetyltransferase (EC 2.3.1.67); the enzymes of the 'de novo' pathway: 1-O-alkyl-2-lyso-sn-glycero-3-phosphate (alkyl-lyso-GP):acetyl-CoA acetyltransferase and 1-O-alkyl-2-acetyl-sn-glycerol (alkylacetyl-G):CDP-choline cholinephosphotransferase (EC 2.7.8.16); and some enzymes involved in the catabolism of PAF and lyso-PAF were assayed. Only the enzymes of the 'de novo' pathway and small amounts of PAF acetylhydrolase, phospholipase A2 and a lysophospholipase D acting on either lipids could be detected in the gastric preparations, whereas lyso-PAF:acetyl-CoA acetyltransferase activity was undetectable. The specific activity of alkyl-lyso-GP:acetyl-CoA acetyltransferase in the gastric mucosa was about one-tenth of that found in spleen microsomes and its apparent Km for acetyl-CoA was 454 microM compared with 277 microM in spleen microsomes. Glandular mucosa homogenates contained preformed PAF at a concentration of 2.7 +/- 0.7 ng equivalents of PAF (hexadecyl)/mg of protein. When gastric microsomes were incubated with micromolar concentrations of fattyacids (arachidonic, palmitic and oleic) prior to the assay of dithiothreitol (DTT)-insensitive cholinephosphotransferase, a dose-dependent reduction in the formation of PAF was observed, arachidonic acid being the most potent inhibitor, followed by linoleic acid (only tested on spleen microsomes) and oleic acid. By contrast, 1,2-diolein and phosphatidylcholine (dipalmitoyl) showed no or little effect. These results indicate that glandular gastric mucosa can produce PAF through the 'de novo' pathway, and that fattyacids, especially unsaturated, can reduce that synthesis by

From their phylogenetic and pharmacological classification it might be inferred that cannabinoid receptors and their endogenous ligands constitute a rather specialised and biologically distinct signalling system. However, the opposite is true and accumulating data underline how much the endocannabinoid system is intertwined with other lipid and non-lipid signalling systems. Endocannabinoids per se have many structural congeners, and these molecules exist in dynamic equilibria with different other lipid-derived mediators, including eicosanoids and prostamides. With multiple crossroads and shared targets, this creates a versatile system involved in fine-tuning different physiological and metabolic processes, including inflammation. A key feature of this 'expanded' endocannabinoid system, or 'endocannabinoidome', is its subtle orchestration based on interactions between a relatively small number of receptors and multiple ligands with different but partly overlapping activities. Following an update on the role of the 'endocannabinoidome' in inflammatory processes, this review continues with possible targets for intervention at the level of receptors or enzymes involved in formation or breakdown of endocannabinoids and their congeners. Although its pleiotropic character poses scientific challenges, the 'expanded' endocannabinoid system offers several opportunities for prevention and therapy of chronic diseases. In this respect, successes are more likely to come from 'multiple-target' than from 'single-target' strategies. PMID:26325095

Microbial biosynthesis of fattyacid-like chemicals from renewable carbon sources has attracted significant attention in recent years. Free fattyacids can be used as precursors for the production of fuels or chemicals. Free fattyacids can be produced by introducing an acyl-acyl carrier protein thioesterase gene into Escherichia coli. The presence of the acyl-ACP thioesterase will break the fattyacid elongation cycle and release free fattyacid. Depending on their sequence similarity and substrate specificity, class FatA thioesterase is active on unsaturated acyl-ACPs and class FatB prefers saturated acyl group. Different acyl-ACP thioesterases have different degrees of chain length specificity. Although some of these enzymes have been characterized from a number of sources, information on their ability to produce free fattyacid in microbial cells has not been extensively examined until recently. In this study, we examined the effect of the overexpression of acyl-ACP thioesterase genes from Diploknema butyracea, Gossypium hirsutum, Ricinus communis and Jatropha curcas on free fattyacid production. In particular, we are interested in studying the effect of different acyl-ACP thioesterase on the quantities and compositions of free fattyacid produced by an E. coli strain ML103 carrying these constructs. It is shown that the accumulation of free fattyacid depends on the acyl-ACP thioesterase used. The strain carrying the acyl-ACP thioesterase gene from D. butyracea produced approximately 0.2g/L of free fattyacid while the strains carrying the acyl-ACP thioesterase genes from R. communis and J. curcas produced the most free fattyacid at a high level of more than 2.0 g/L at 48 h. These two strains accumulated three major straight chain free fattyacids, C14, C16:1 and C16 at levels about 40%, 35% and 20%, respectively. PMID:22001432

Coconut oil is a rich source of beneficial medium chain fattyacids (MCFAs) particularly lauric acid. In this study, the oil was modified into a value-added product using direct modification of substrate through fermentation (DIMOSFER) method. A coconut-based and coconut-oil-added solid-state cultivation using a Malaysian lipolytic Geotrichum candidum was used to convert the coconut oil into MCFAs-rich oil. Chemical characteristics of the modified coconut oils (MCOs) considering total medium chain glyceride esters were compared to those of the normal coconut oil using ELSD-RP-HPLC. Optimum amount of coconut oil hydrolysis was achieved at 29% moisture content and 10.14% oil content after 9 days of incubation, where the quantitative amounts of the modified coconut oil and MCFA were 0.330 mL/g of solid media (76.5% bioconversion) and 0.175 mL/g of solid media (53% of the MCO), respectively. MCOs demonstrated improved antibacterial activity mostly due to the presence of free lauric acid. The highest MCFAs-rich coconut oil revealed as much as 90% and 80% antibacterial activities against Staphylococcus aureus and Escherichia coli, respectively. The results of the study showed that DIMOSFER by a local lipolytic G. candidum can be used to produce MCFAs as natural, effective, and safe antimicrobial agent. The produced MCOs and MCFAs could be further applied in food and pharmaceutical industries. PMID:23971051

A short-term feeding paradigm in mice, with diets enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), was used to study the modulation of T cell activation via the T cell receptor (TcR) and the downstream pathways of intracellular signaling. Diets enriched in EPA and DHA suppressed antigen-specific delayed hypersensitivity reactions and mitogen-induced proliferation of T cells. Cocultures of accessory cells and T cells from mice given different diets revealed that purified fattyacid ethyl esters acted directly on the T cell, rather than through the accessory cell. The loss of proliferative capacity was accompanied by reductions in interleukin (IL)-2 secretion and IL-2 receptor alpha chain mRNA transcription, suggesting that dietary EPA and DHA act, in part, by interrupting the autocrine IL-2 activation pathway. Dietary EPA and DHA blunted the production of intracellular second messengers, including diacylglycerol and ceramide, following mitogen stimulation in vitro. Dietary effects appear to vary with the agonist employed (i.e., anti-CD3 [TcR], anti-CD28, exogenous IL-2, or phorbol myristate acetate and ionomycin). PMID:10944491

Objective The aim of this study was to evaluate the antifungal activity of the major fraction of fattyacids methyl esters (FAMEs) isolated from Linum usitatissimum L. seeds oil collected from Bechar department (Algeria). Methods The assessment of antifungal activity was carried out in terms of percentage of radial growth on solid medium (potatoes dextrose agar PDA) and biomass growth inhibition on liquid medium (potatoes dextrose broth PDB) against two fungi. Results The FAMEs was found to be effective in inhibiting the radial mycelial growth of Aspergillus flavus more than Aspergillus ochraceus on all tested concentrations. The highest antifungal index was found to be (54.19%) compared to Aspergillus ochraceus (40.48%). The results of the antifungal activity of the FAMEs inhibition of biomass on liquid medium gave no discounted results, but this does not exclude the antifungal activity. Conclusions We can assume that the observed antifungal potency may be due to the abundance of linoleic and α-linolenic acids in linseed oil which appears to be promising to treat fungal infections, storage fungi and food spoilage in food industry field. PMID:23730556

Fattyacids are a promising raw material for substance production because of their highly reduced and anhydrous nature, which can provide higher fermentation yields than sugars. However, they are insoluble in water and are poorly utilized by microbes in industrial fermentation production. We used fattyacids as raw materials for L-lysine fermentation by emulsification and improved the limited fattyacid-utilization ability of Escherichia coli. We obtained a fattyacid-utilizing mutant strain by laboratory evolution and demonstrated that it expressed lower levels of an oxidative-stress marker than wild type. The intracellular hydrogen peroxide (H₂O₂) concentration of a fattyacid-utilizing wild-type E. coli strain was higher than that of a glucose-utilizing wild-type E. coli strain. The novel mutation rpsA(D210Y) identified in our fattyacid-utilizing mutant strain enabled us to promote cell growth, fatty-acid utilization, and L-lysine production from fattyacid. Introduction of this rpsA(D210Y) mutation into a wild-type strain resulted in lower H₂O₂ concentrations. The overexpression of superoxide dismutase (sodA) increased intracellular H₂O₂ concentrations and inhibited E. coli fatty-acid utilization, whereas overexpression of an oxidative-stress regulator (oxyS) decreased intracellular H₂O₂ concentrations and promoted E. coli fattyacid utilization and L-lysine production. Addition of the reactive oxygen species (ROS) scavenger thiourea promoted L-lysine production from fattyacids and decreased intracellular H₂O₂ concentrations. Among the ROS generated by fatty-acid β-oxidation, H₂O₂ critically affected E. coli growth and L-lysine production. This indicates that the regression of ROS stress promotes fattyacid utilization, which is beneficial for fattyacids used as raw materials in industrial production. PMID:24169950

Tocopherol can inhibit the oxidative degradation of polyunsaturated fattyacids by stabilizing lipid radicals that form at elevated temperatures or pro-oxidant conditions. This is particularly relevant for feeds formulated with fattyacids such as docosahexaenoic acid (DHA) or linolenic acid (ALA) T...

In the presence of surfactant sodium dodecylbenzene sulfonate (SDBS) the hydrolysis products accumulation and the short-chain fattyacids (SCFA) production during waste activated sludge fermentation under mesophilic and thermophilic conditions was compared with that at room temperature. In order to understand the mechanism of significant amounts of mesophilic and thermophilic hydrolysis products and SCFA observed in the presence of surfactant, the kinetic models at different SDBS dosages were developed. It was found that SDBS increased the mesophilic and thermophilic hydrolysis rate significantly, and the maximum specific utilization of hydrolysis products increased at low SDBS and decreased at high one. However, the observed maximum specific utilization of SCFA decreased seriously with SDBS increase. In the presence of SDBS the decay rate of acidogenic bacteria not only was lower than that in the absence of SDBS but decreased with the increase of SDBS under either mesophilic or thermophilic conditions. PMID:20409704

In this study, the selective hydrogenation of fattyacids to fatty alcohols can be achieved under moderate conditions (180 °C, 30 bar H2) by simultaneously supporting copper and iron oxides on mesoporous silica nanoparticles. The activity of the cosupported oxides is significantly higher than that of each supported metal oxide and of a physical mixture of both individually supported metal oxides. A strong interaction between both metal oxides is evident from dispersion, XRD, TPR, and acetic acid TPD measurements, which is likely responsible for the synergistic behavior of the catalyst. Copper oxide is reduced in situ to its metallic formmore » and thereby activates hydrogen.« less

In this study, the selective hydrogenation of fattyacids to fatty alcohols can be achieved under moderate conditions (180 °C, 30 bar H2) by simultaneously supporting copper and iron oxides on mesoporous silica nanoparticles. The activity of the cosupported oxides is significantly higher than that of each supported metal oxide and of a physical mixture of both individually supported metal oxides. A strong interaction between both metal oxides is evident from dispersion, XRD, TPR, and acetic acid TPD measurements, which is likely responsible for the synergistic behavior of the catalyst. Copper oxide is reduced in situ to its metallic form and thereby activates hydrogen.

Free nitrous acid (FNA) serving as a pretreatment is an effective approach to accelerate sludge disintegration. Also, sodium dodecylbenzene sulfonate (SDBS), a type of surfactants, has been determined at significant levels in sewage sludge, which thereby affects the characteristics of sludge. Both FNA pretreatment and sludge SDBS levels can affect short-chain fattyacid (SCFA) generation from sludge anaerobic fermentation. To date, however, the combined effect of FNA pretreatment and SDBS presence on SCFA production as well as the corresponding mechanisms have never been documented. This work therefore aims to provide such support. Experimental results showed that the combination of FNA and SDBS treatment not only improved SCFA accumulation but also shortened the fermentation time. The maximal SCFA accumulation of 334.5 mg chemical oxygen demand (COD)/g volatile suspended solids (VSS) was achieved at 1.54 mg FNA/L treatment and 0.02 g/g dry sludge, which was respectively 1.79-fold and 1.41-fold of that from FNA treatment and sludge containing SDBS alone. Mechanism investigations revealed that the combined FNA pretreatment and SDBS accelerated solubilization, hydrolysis, and acidification steps but inhibited the methanogenesis. All those observations were in agreement with SCFA enhancement. PMID:26868898